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Vasodilatation
Kinds of Vasodilatation Selected AbstractsInterobserver and Intraobserver Variability of Flow-Mediated Vasodilatation of the Brachial ArteryECHOCARDIOGRAPHY, Issue 1 2008Iana Simova M.D. Flow-mediated endothelial-dependent vasodilatation (FMD) of the brachial artery is a method capable of detecting endothelial dysfunction. In order to implement this method in future clinical research studies, its reproducibility and precision have to be assessed. The aim of the study is to evaluate the inter- and intraobserver variability of FMD performed in our department. We investigate 40 patients. FMD is measured by two independent observers to test the interobserver variability, and repeated by the first observer to test the intraobserver variability. We compare the baseline and post-ischemic diameter of the brachial artery and the percent dilatation. The correlation coefficients for these comparisons are high (>0.92) with a significance of less than 0.001. The inter- and intraobserver variability is further tested comparing the mean values of the baseline and post ischemic diameter of the brachial artery and the percent dilatation. The absolute values of the mean paired differences and the standard deviations (SDs) of the differences are 0.02850 ± 0.05942, P = 0.004, 0.01175 ± 0.08177, P = 0.369 and 0.28375 ± 1.61561, P = 0.273, respectively for the interobserver variability and 0.00475 ± 0.04663, P = 0.523, 0.00050 ± 0.05267, P = 0.952 and 0.15725 ± 1.19922, P = 0.412, respectively for the intraobserver variability. It can be concluded that the inter- and intraobserver variability for FMD performed in our department is acceptable. FMD can be performed precisely and accurately, with a satisfactory reproducibility and can be safely and reliably implemented in future clinical research studies. [source] UPREGULATED ENDOTHELIN SYSTEM IN DIABETIC VASCULAR DYSFUNCTION AND EARLY RETINOPATHY IS REVERSED BY CPU0213 AND TOTAL TRITERPENE ACIDS FROM FRUCTUS CORNICLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2007Wei Su SUMMARY 1The aims of the present study were to examine whether: (i) upregulation of the endothelin (ET) pathway is involved in impairment of vascular relaxation and early retinopathy in diabetic rats; and (ii) vascular and retinal abnormalities respond to the total triterpene acid (TTA) isolated from Fructus Corni compared with responses to the novel endothelin receptor antagonist CPU0213 and aminoguanidine (AMG), a special antagonist for advanced glycation end-products (AGE) and inducible nitric oxide synthase (iNOS). 2Male Sprague-Dawley rats were randomized into five groups, namely a normal control and four diabetic groups, which included an untreated diabetic group and groups treated with AMG (100 mg/kg, i.g.), CPU0213 (30 mg/kg, s.c.) or TTA (50 mg/kg, i.g.). Diabetes was induced by single injection of streptozotocin (60 mg/kg, i.p.) on the 1st day. The mRNA expression of prepro-endothelin-1 (ppET-1), endothelin-converting enzyme (ECE) and iNOS in the thoracic aorta and mRNA for ETA receptors and iNOS in the retina were detected by reverse transcription,polymerase chain reaction. Vasorelaxation to acetylcholine (ACh) and functional assessment of nitric oxide (NO) bioavailability was determined in the thoracic aorta. 3We observed upregulated mRNA expression of iNOS, ppET-1 and ECE in the thoracic aorta and upregulated mRNA for the ETA receptor and iNOS in the retina in the untreated diabetic group. Vasodilatation mediated by ACh and NO bioavailability were markedly reduced in the thoracic aorta compared with the normal control group. These abnormalities were essentially reversed by TTA, CPU0213 or AMG, with the exception with that AMG did not modify vasodilatation to ACh. 4These data suggest that upregulation of gene transcription of the ET system mediates depressed vasorelaxation, NO bioavailability and changes in iNOS and ETA receptors that reflect early retinopathy in diabetic rats. Total triterpene acid, in terms of pharmacological properties resembling the endothelin receptor antagonist CPU0213, is effective in normalizing expression of the ET system and iNOS in early diabetic retinopathy and vasculaopathy. [source] Endothelin attenuates endothelium-dependent platelet inhibition in manACTA PHYSIOLOGICA, Issue 4 2010R. E. Malmström Abstract Aim:, The vascular endothelium produces several substances, including nitric oxide (NO) and endothelin-1 (ET-1), which participate in the regulation of vascular tone in humans. Both these substances may exert other actions of importance for cardiovascular disease, e.g. effects on vascular smooth muscle cell proliferation and inflammation, and NO inhibits platelet function. Experiments were designed to investigate the effect of ET-1 on endothelium-dependent vasodilatation and attenuation of platelet activation. Methods:, In 25 healthy male subjects (25 ± 1 years), forearm blood flow was measured by venous occlusion plethysmography, and platelet activity was assessed by whole blood flow cytometry (platelet fibrinogen binding and P-selectin expression) in unstimulated and adenosine diphosphate (ADP)-stimulated samples during administration of ET-1, the endothelium-dependent vasodilator acetylcholine and the NO synthase inhibitor l -NMMA. Results:, Acetylcholine increased forearm blood flow and significantly inhibited platelet activation in both unstimulated and ADP-stimulated samples. In samples stimulated with 0.3 ,m ADP, fibrinogen binding decreased from 41 ± 4% to 31 ± 3% (P < 0.01, n = 11) after acetylcholine administration. The vasodilator response to acetylcholine was significantly impaired during infusions of ET-1 and l -NMMA. ET-1 did not affect platelet activity per se, whereas l -NMMA increased platelet P-selectin expression. Both ET-1 and l -NMMA attenuated the acetylcholine-induced inhibition of platelet activity. Conclusions:, Our study indicates that, further to inhibiting endothelium-dependent vasodilatation, ET-1 may also attenuate endothelium-dependent inhibition of platelet activation induced by acetylcholine. An enhanced ET-1 activity, as suggested in endothelial dysfunction, may affect endothelium-dependent platelet modulation and thereby have pathophysiological implications. [source] Effects of C-peptide on forearm blood flow and brachial artery dilatation in patients with type 1 diabetes mellitusACTA PHYSIOLOGICA, Issue 3 2001E. Fernqvist-Forbes Recent studies suggest that C-peptide increases blood flow in both exercising and resting forearm in patients with type 1 diabetes. Now we have studied the effect of C-peptide administration on endothelial-mediated and non-endothelial-mediated arterial responses as well as central haemodynamics in 10 patients with type 1 diabetes in a placebo-controlled double-blind study. Euglycaemia was maintained with an i.v. insulin infusion before and during the study. A high-resolution ultrasound technique and Doppler echocardiography were used to assess haemodynamic functions. Brachial artery blood flow and brachial artery diameter were measured in the basal state, 1 and 10 min after reactive hyperaemia and 4 min after sublingual glyceryl trinitrate administration (GTN; endothelial-independent vasodilatation), both before and after the end of 60-min C-peptide (6 pmol kg,1 min,1) or saline infusion periods. Echocardiographic measurements were also performed before and at the end of the infusion periods. Seven healthy age-matched males served as controls for vascular studies. The patients showed a blunted brachial dilatation after reactive hyperaemia in comparison with the healthy controls (2.1 ± 0.5% vs. 9.3 ± 0.3%, P < 0.001), indicating a disturbed endothelial function. C-peptide infusion compared with saline resulted in increased basal blood flow (33 ± 6%, P < 0.001) and brachial arterial dilatation (4 ± 1%, P < 0.05). Left ventricular ejection fraction seemed to be improved (5 ± 2%, P < 0.05) at the end of C-peptide infusion compared with placebo. The vascular response to reactive hyperaemia and GTN was not affected by C-peptide infusion. Our results demonstrate that physiological concentrations of C-peptide increase resting forearm blood flow, brachial artery diameter and left ventricular systolic function in patients with type 1 diabetes. [source] Forearm vascular and neuroendocrine responses to graded water immersion in humansACTA PHYSIOLOGICA, Issue 2 2000Gabrielsen The hypothesis that graded expansion of central blood volume by water immersion to the xiphoid process and neck would elicit a graded decrease in forearm vascular resistance was tested. Central venous pressure increased (P < 0.05) by 4.2 ± 0.4 mmHg (mean ± SEM) during xiphoid immersion and by 10.4 ± 0.5 mmHg during neck immersion. Plasma noradrenaline was gradually suppressed (P < 0.05) by 62 ± 8 and 104 ± 11 pg mL,1 during xiphoid and neck immersion, respectively, indicating a graded suppression of sympathetic nervous activity. Plasma concentrations of arginine vasopressin were suppressed by 1.5 ± 0.5 pg mL,1 (P < 0.05) during xiphoid immersion and by 2.0 ± 0.5 pg mL,1 during neck immersion (P < 0.05 vs. xiphoid immersion). Forearm subcutaneous vascular resistance decreased to the same extent by 26 ± 9 and 28 ± 4% (P < 0.05), respectively, during both immersion procedures, whereas forearm skeletal muscle vascular resistance declined only during neck immersion by 27 ± 6% (P < 0.05). In conclusion, graded central blood volume expansion initiated a graded decrease in sympathetic nervous activity and AVP-release. Changes in forearm subcutaneous vascular resistance, however, were not related to the gradual withdrawal of the sympathetic and neuroendocrine vasoconstrictor activity. Forearm skeletal muscle vasodilatation exhibited a more graded response with a detectable decrease only during immersion to the neck. Therefore, the forearm subcutaneous vasodilator response reaches saturation at a lower degree of central volume expansion than that of forearm skeletal muscle. [source] 2,2,-Nitrophenylisatogen potentiates P2X1 receptor mediated vascular contraction and blood pressure elevationDRUG DEVELOPMENT RESEARCH, Issue 1 2003Anna-Karin Wihlborg Abstract The objective of this research was to examine the effects of chemical compounds with possible P2 receptor modulating effects and to characterize the potentiating effects of 2,2,-nitrophenylisatogen (NPI) on P2X1 receptors in vitro and in vivo. Chemical compounds were tested in an in vitro pharmacological assay using vascular segments from the rat mesenteric artery stimulated by P2 receptor-specific agonists. Contractions were expressed as a percentage of 60 mM K+ -induced contractions. Blood pressure was evaluated in pithed rats. NPI (30 ,M) added 15 min before addition of the P2X1 receptor-specific agonist ,,-MeATP increased the maximum vasoconstriction from 23% to 49% (an increase of 113%). Furthermore, NPI prevented the desensitization of repeated ,,-MeATP contractions. Related compounds were examined, and 2-(3-methoxy-phenyl)-1-oxy-indol-3-one (MPI) had similar effects as NPI, but several others lacked effect. NPI had no effect on ADP,S (P2Y1) or acetylcholine-mediated vasodilatation, nor on UTP (P2Y2/4), UDP (P2Y6), or noradrenaline-mediated contractions. In pithed rats, the blood pressure response to 50 nmol/kg-infusion of ,,-MeATP was increased from 50±6 to 63±5 mmHg (P<0.05), but had no effect on basal blood pressure or on the cardiovascular response to preganglionic nerve stimulation. In conclusion, NPI and MPI potentiates P2X1 receptor vascular contractions in vitro and (NPI) blood pressure effects in vivo. It is possible that the effect is mediated by an inhibition of P2X1 receptor desensitization. Drug Dev. Res. 59:82,87, 2003. © 2003 Wiley-Liss, Inc. [source] Expanding field of purinergic signalingDRUG DEVELOPMENT RESEARCH, Issue 1-2 2001Geoffrey Burnstock Abstract This article attempts to paint a broad picture of the extraordinary explosive recent developments in the purinergic signaling field. After a brief historical review and update of purinoceptor subtypes, the focus is on the physiological roles of purines and pyrimidines. These are considered both in terms of short-term signaling in neurotransmission, secretion, and vasodilatation and in long-term (trophic) signaling in development, regeneration, proliferation, and cell death. Examples of trophic signaling include cartilage development in limb buds, glial cell proliferation, development of skeletal muscle, changes in receptor expression in smooth-muscle phenotypes, maturation of testicular spermatids, and bone remodeling. Plasticity of purinoceptor expression in pathological conditions is described, including the increase in the purinergic component of parasympathetic nervous control of the human bladder in interstitial cystitis and outflow obstruction and in sympathetic cotransmitter control of blood vessels in hypertensive rats, the appearance of P2X7 receptors in the glomeruli of the kidney from diabetic and transgenic hypertensive animal models, and up-regulation of P2X1 and P2Y2 receptor mRNA in hearts of rats with congestive heart failure. The role of P2X3 receptors in nociception is considered, and a new hypothesis about purinergic mechanosensory transduction in the gut is explored. A personal view of some of the areas ripe for future development concludes this article, including a discussion of different strategies that could lead to the development of purinergic therapeutic agents. Drug Dev. Res. 52:1,10, 2001. © 2001 Wiley-Liss, Inc. [source] Association between Endothelial Function and Chronotropic Incompetence in Subjects with Chronic Heart Failure Receiving Optimal Medical TherapyECHOCARDIOGRAPHY, Issue 3 2010M.D., Timothy J. Vittorio M.S. Objective: Impairment of flow-mediated, endothelium-dependent vasodilatation (FMD) of the brachial artery identifies peripheral endothelial dysfunction in subjects with chronic congestive heart failure (CHF) and is associated with increased morbidity and mortality. To further elucidate the interaction of peripheral and central mechanisms in the syndrome of CHF, we examined the association between endothelial function and chronotropic incompetence, an emerging prognostic marker in CHF. Methods: Thirty subjects with stable New York Heart Association (NYHA) functional class II,III CHF were studied. A vascular ultrasound study was performed to measure brachial artery FMD. The percentage of age-adjusted maximal predicted heart rate (MPHR) reached during cardiopulmonary exercise tolerance testing (CPETT) was used to assess the degree of chronotropic competence. All patients received ACE inhibitors and ,-adrenoceptor blockers. Results: Brachial artery FMD averaged 1.3 ± 2.4% and age-adjusted % MPHR 74.1 ± 11.7%. FMD correlated with % MPHR among all patients (r = 0.60, P = 0.01). FMD and resting heart rate (RHR) did not significantly correlate (r = 0.13, P = 0.55). Conclusions: FMD, a measure of peripheral endothelial dysfunction, and % MPHR, a central determinant of cardiac output, are moderately correlated in heart failure patients receiving optimal medical therapy. Whether a cause-effect relationship underlies this association remains to be investigated. (Echocardiography 2010;27:294-299) [source] Effect of Sildenafil Citrate (Viagra) on Coronary Flow in Normal SubjectsECHOCARDIOGRAPHY, Issue 1 2008Fuminobu Ishikura M.D. Background: The purpose of this study was to evaluate the effect of sildenafil citrate (Viagra) on coronary function in normal subjects. Methods: The study assessed mean blood pressure, left anterior descending coronary artery (LAD) flow, and echocardiographic variables before and 30 and 60 minutes after taking 50 mg of sildenafil citrate. The mean velocity of LAD flow was assessed with Doppler flow imaging. The study subjects were 6 healthy male volunteers (mean age 37 years). Results: The mean velocity of LAD flow increased 60 minutes after taking sildenafil citrate, but there were no other changes. Two volunteers felt mild flashing and one had mild headache during the study. Conclusion: Sildenafil citrate caused vasodilatation in a normal coronary artery without systemic pressure drops. These results suggest that the agent itself did not have negative effects on the heart in normal subjects. [source] Interobserver and Intraobserver Variability of Flow-Mediated Vasodilatation of the Brachial ArteryECHOCARDIOGRAPHY, Issue 1 2008Iana Simova M.D. Flow-mediated endothelial-dependent vasodilatation (FMD) of the brachial artery is a method capable of detecting endothelial dysfunction. In order to implement this method in future clinical research studies, its reproducibility and precision have to be assessed. The aim of the study is to evaluate the inter- and intraobserver variability of FMD performed in our department. We investigate 40 patients. FMD is measured by two independent observers to test the interobserver variability, and repeated by the first observer to test the intraobserver variability. We compare the baseline and post-ischemic diameter of the brachial artery and the percent dilatation. The correlation coefficients for these comparisons are high (>0.92) with a significance of less than 0.001. The inter- and intraobserver variability is further tested comparing the mean values of the baseline and post ischemic diameter of the brachial artery and the percent dilatation. The absolute values of the mean paired differences and the standard deviations (SDs) of the differences are 0.02850 ± 0.05942, P = 0.004, 0.01175 ± 0.08177, P = 0.369 and 0.28375 ± 1.61561, P = 0.273, respectively for the interobserver variability and 0.00475 ± 0.04663, P = 0.523, 0.00050 ± 0.05267, P = 0.952 and 0.15725 ± 1.19922, P = 0.412, respectively for the intraobserver variability. It can be concluded that the inter- and intraobserver variability for FMD performed in our department is acceptable. FMD can be performed precisely and accurately, with a satisfactory reproducibility and can be safely and reliably implemented in future clinical research studies. [source] A diet enriched with mackerel (Scomber scombrus),derived products improves the endothelial function in a senior population (Prevención de las Enfermedades Cardiovasculares: Estudio Santoña , PECES project)EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2009J. R. De Berrazueta ABSTRACT Background, Regular consumption of fish reduces cardiovascular risks. Here, we investigate if the consumption of products with mackerel (Scomber scombrus) with 8·82 g of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) content per 100 g of product improves parameters of endothelial function in a controlled population. Materials and methods, Subjects maintained a 12-week diet with products with mackerel. The population consisted of 58 senior subjects (12 withdrawals, 25 women), aged 82·08 ± 8·13 years (Group A). Twenty-three senior subjects (13 women) on a regular diet were used as the control group (Group B). Subjects of Group A received 57 portions throughout 12 weeks (four to five portions a week of products with a mean EPA + DHA content of 2·5 g a day). A continuous follow-up and a final evaluation were performed to determine the level of consumption. Plasma samples were stored at ,70 °C for a biochemical study. Endothelial function was analysed by reactive hyperemia with a mercury strain gauge plethysmography with measurement of blood flow in the forearm, both baseline and at the end of the 12-week diet. Results, Endothelium-dependent vasodilatation significantly increased in Group A subjects (P < 0·001). No changes were found in Group B. The subgroup analyses showed that improvements were produced in Group A subjects without cardiovascular disease (P < 0·001). Nitrites/nitrates and von Willebrand factor plasma concentrations were higher in participants after the 12-week diet. Conclusions, The consumption of mackerel meat products improves endothelium-dependent, flow-mediated vasodilatation in a senior population. This finding might explain some of the cardioprotective effects of fish consumption. [source] Fatty acid incorporation in endothelial cells and effects on endothelial nitric oxide synthaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2007S. Couloubaly Abstract Background The nature of fatty acids provided by the diet as well as plasma lipid metabolism can modify the composition and properties of plasma membrane and thus the activity of membrane proteins. In humans, as well as in experimental models, diabetes is associated with both an alteration in serum lipid profile and a documented endothelial dysfunction. This in vitro study investigated on an immortalized human endothelial cell line (EA.hy 926) the specific effects of several free fatty acids (FFAs) on the composition of cellular membranes and the regulation of endothelial nitric oxide synthase (eNOS). Materials and methods 0·1% of lipid deprived serum was added to the incubation medium with 25 mm glucose in order to study the effects of individual fatty acids: myristic acid, palmitic acid, stearic acid, oleic acid or linoleic acid at 100 µm bound with albumin. The effects of the FFAs on the endothelial nitric oxide synthase were investigated on mRNA level by quantitative PCR, on protein level and Ser1177 phosphorylation by Western blot and on enzymatic activity on living cells using radiolabelled arginine. Results Free linoleic acid increased the membrane content in n-6 fatty acids (mainly C18: n-6 and its metabolites) with a decrease in saturated and monounsaturated fatty acids. These conditions decreased the basal eNOS activity and reduced the phosphorylation of eNOS-Ser1177 due to activation by histamine. Free palmitic acid enriched the membranes with 16 : 0 with a slight decrease in monounsaturated fatty acids. These conditions increased eNOS activation without increasing Ser1177 phosphorylation upon histamine activation. The addition of the other FFAs also resulted in modifications of membrane composition, which did not to affect eNOS-Ser1177 phosphorylation. Conclusion Among the fatty acids used, only modification of the membrane composition due to linoleic acid supply disturbed the basal enzymatic activity and Ser1177 phosphorylation of eNOS in a way that limited the role of histamine activation. Linoleic acid might involve the dysfunction of both eNOS basal activity and its phosphorylation status and may then contribute to an impaired vasodilatation in vivo. [source] Enhanced external counterpulsation improves skin oxygenation and perfusionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2004M. J. Hilz Abstract Background, Enhanced external counterpulsation (EECP) augments diastolic and reduces systolic blood pressures. Enhanced external counterpulsation has been shown to improve blood flow in various organ systems. Beneficial effects on skin perfusion might allow EECP to be used in patients with skin malperfusion problems. This study was performed to assess acute effects of EECP on superficial skin blood flow, transdermal oxygen and carbon dioxide pressures. Materials and methods, We monitored heart rate, blood pressure, transdermal blood flow as well as oxygen and carbon dioxide pressures in 23 young, healthy persons (28 ± 4 years) and 15 older patients (64 ± 7 years) with coronary artery disease before, during and 3 min after 5 min EECP. Friedman test was used to compare the results of 90-s epochs before, during and after EECP. Significance was set at P < 0·05. Results, Enhanced external counterpulsation increased heart rate and mean blood pressure. During EECP, transdermal oxygen pressure and concentration of moving blood cells increased while transdermal carbon dioxide pressure and velocity of moving blood cells decreased significantly in both groups. After EECP, transdermal carbon dioxide pressure was still reduced while the other parameters returned to baseline values. Conclusions, Improved skin oxygenation and carbon dioxide clearance during EECP seem to result from the increased concentration and reduced flow velocity, i.e. prolonged contact time, of erythrocytes. The increased concentration of moving blood cells and the decreased velocity of moving blood cells at both tested skin sites indicate peripheral vasodilatation. [source] Individuals at increased coronary heart disease risk are characterized by an impaired microvascular function in skinEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2003R. G. IJzerman Abstract Background To investigate whether microvascular function in skin is a valid model to study the relationships between cardiovascular risk factors and microvascular function, we investigated skin microvascular function in individuals with increased coronary heart disease (CHD) risk. Materials and methods Forty-six healthy White individuals aged 30,70 years were studied. Coronary heart disease risk was assessed with the use of the CHD risk score according to the Framingham Heart Study, which is based on the risk factors age, blood pressure, cigarette smoking, total cholesterol, HDL cholesterol and diabetes. Endothelium-dependent and -independent vasodilation in skin were evaluated with laser Doppler after iontophoresis of acetylcholine and sodium nitroprusside. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. Results Coronary heart disease risk score (i.e. the 10-year probability of CHD) varied from 1,37%. Microvascular function decreased with increasing quartiles of CHD risk (for acetylcholine-mediated vasodilation: 687, 585, 420 and 326%, P = 0·002; for nitroprusside-mediated vasodilation: 776, 582, 513 and 366%, P = 0·02; for capillary recruitment: 49·9, 44·6, 27·2 and 26·7%, P = 0·001). These trends were similar in men and women (P for interaction > 0·2) and independent of body mass index. Conclusions Increased CHD risk is associated with an impaired endothelium-dependent vasodilatation and capillary recruitment in skin, suggesting that microvascular function in skin is a valid model to study the relationships between cardiovascular risk factors and microvascular function. [source] Regulation of cerebral blood flow in mammals during chronic hypoxia: a matter of balanceEXPERIMENTAL PHYSIOLOGY, Issue 2 2010Philip N. Ainslie Respiratory-induced changes in the partial pressures of arterial carbon dioxide and oxygen play a major role in cerebral blood flow (CBF) regulation. Elevations in (hypercapnia) lead to vasodilatation and increases in CBF, whereas reductions in (hypocapnia) lead to vasoconstriction and decreases in CBF. A fall in (hypoxia) below a certain threshold (<40,45 mmHg) also produces cerebral vasodilatation. Upon initial exposure to hypoxia, CBF is elevated via a greater relative degree of hypoxia compared with hypocapnia. At this point, hypoxia-induced elevations in blood pressure and loss of cerebral autoregulation, stimulation of neuronal pathways, angiogenesis, release of adenosine, endothelium-derived NO and a variety of autocoids and cytokines are additional factors acting to increase CBF. Following 2,3 days, however, the process of ventilatory acclimatization results in a progressive rise in ventilation, which increases and reduces , collectively acting to attenuate the initial rise in CBF. Other factors acting to lower CBF include elevations in haematocrit, sympathetic nerve activity and local and endothelium-derived vasoconstrictors. Hypoxia-induced alterations of cerebrovascular reactivity, autoregulation and pulmonary vascular tone may also affect CBF. Thus, the extent of change in CBF during exposure to hypoxia is dependent on the balance between the myriad of vasodilators and constrictors derived from the endothelium, neuronal innervations and perfusion pressure. This review examines the extent and mechanisms by which hypoxia regulates CBF. Particular focus will be given to the marked influence of hypoxia associated with exposure to high altitude and chronic lung disease. The associated implications of these hypoxia-induced integrative alterations for the regulation of CBF are discussed, and future avenues for research are proposed. [source] Tissue-specific regulation of ACE/ACE2 and AT1/AT2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor-, knock-out miceEXPERIMENTAL PHYSIOLOGY, Issue 5 2008K. Bridget Brosnihan Angiotensin-converting enzyme (ACE) and ACE2 and the AT1 and AT2 receptors are pivotal points of regulation in the renin,angiotensin system. ACE and ACE2 are key enzymes in the formation and degradation of angiotensin II (Ang II) and angiotensin-(1,7)(Ang-(1,7)). Ang II acts at either the AT1 or the AT2 receptor to mediate opposing actions of vasoconstriction or vasodilatation respectively. While it is known that oestrogen acts to downregulate ACE and the AT1 receptor, its regulation of ACE2 and the AT2 receptor and the involvement of a specific oestrogen receptor subtype are unknown. To investigate the role of oestrogen receptor-, (ER,) in the regulation by oestrogen of ACE/ACE2 and AT1/AT2 mRNAs in lung and kidney, ovariectomized female mice lacking apolipoprotein E (ee) with the ER, (AAee) or without the ER, (,,ee) were treated with 17,-oestradiol (6 ,g day,1) or placebo for 3 months. ACE, ACE2, AT1 receptor and AT2 receptor mRNAs were measured using reverse transcriptase, real-time polymerase chain reaction. In the kidney, 17,-oestradiol showed 1.7-fold downregulation of ACE mRNA in AAee mice, with 2.1-fold upregulation of ACE mRNA in ,,ee mice. 17,-Oestradiol showed 1.5- and 1.8-fold downregulation of ACE2 and AT1 receptor mRNA in AAee mice; this regulation was lost in ,,ee mice. 17,-Oestradiol showed marked (81-fold) upregulation of the AT2 receptor mRNA in AAee mice. In the lung, 17,-oestradiol treatment had no effect on AT1 receptor mRNA in AAee mice, but resulted in a 1.5-fold decreased regulation of AT1 mRNA in ,,ee mice. There was no significant interaction of oestrogen with ER, in the lung for ACE, ACE2 and AT2 receptor genes. These studies reveal tissue-specific regulation by 17,-oestradiol of ACE/ACE2 and AT1/AT2 receptor genes, with the ER, receptor being primarily responsible for the regulation of kidney ACE2, AT1 receptor and AT2 receptor genes. [source] The Effect of Progesterone on Coronary Blood Flow in Anaesthetized PigsEXPERIMENTAL PHYSIOLOGY, Issue 1 2001C. Molinari The present study was designed to investigate the effect of progesterone on the coronary circulation and to determine the mechanisms involved. In pigs anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary blood flow caused by intravenous infusion of progesterone at constant heart rate and arterial blood pressure were assessed using an electromagnetic flowmeter. In 14 pigs, infusion of 1 mg h,1 of progesterone caused an increase in coronary blood flow without affecting left ventricular dP/dtmax (rate of change of left ventricular systolic pressure) and filling pressures of the heart. In a further four pigs, this vasodilatory coronary effect was enhanced by graded increases in the dose of the hormone of between 1, 2 and 3 mg h,1. The mechanisms of the above response were studied in the 14 pigs by repeating the experiment after haemodynamic variables had returned to the control values observed before infusion. In six pigs, blockade of muscarinic cholinoceptors and adrenoceptors with atropine, propranolol and phentolamine did not affect the coronary vasodilatation caused by progesterone. In the remaining eight pigs, this response was abolished by intracoronary injection of N, -nitro-L-arginine methyl ester (L-NAME) even when performed after reversing the increase in arterial blood pressure and coronary vascular resistance caused by L-NAME with continuous intravenous infusion of papaverine. The present study showed that intravenous infusion of progesterone primarily caused coronary vasodilatation. The mechanism of this response was shown to involve the endothelial release of nitric oxide. [source] The Neurogenic Vasodilator Response to Endothelin-1: A Study in Human Skin In VivoEXPERIMENTAL PHYSIOLOGY, Issue 6 2000Ruwani Katugampola We have investigated the mediators and mechanisms underlying the vasodilator effects of the potent vasoactive peptide, endothelin-1 (ET-1) and its isomers ET-2 and ET-3 in human skin, in vivo, using cutaneous microdialysis to quantify the release of mediators within the dermal response and scanning laser Doppler imaging to measure changes in blood flux. The effects of local anaesthesia, inhibition of nitric oxide synthase (NOS) by L-NAME and ET receptor blockade on the ET-induced vascular response were also investigated. ET-1, -2 and -3 all caused a dose-dependent area of pallor surrounded by a long-lasting flare which was accompanied by a short-lived burning pruritus. The concentration of nitric oxide (NO) in dialysate collected within the pallor response to 5 ,M ET-1 (1.43 ± 0.64 ,M, n = 5) was not significantly different from baseline levels collected prior to injection (0.86 ± 0.38 ,M) whilst that in the flare increased to reach a peak value of 2.28 ± 0.61 ,M at between 4 and 10 min after intradermal injection (P < 0.004). Pretreatment with local anaesthetic slowed the development of the flare and significantly reduced its size by up to 52% at 20 min after injection (P < 0.05) but had no significant effect on the central pallor. L-NAME, delivered by dialysis also caused a significant reduction in the ET-1-induced flare (P < 0.005). Bosentan, the non-selective ETA/ETB antagonist, when given by dialysis at the site of injection, reduced the area of both the ET-1-induced pallor and surrounding flare by 41 and 26%, respectively. No significant increase in tissue histamine was measured within either the pallor or flare response to ET-1, -2 or -3. Together these data confirm that the vasodilator response to endothelin-1 in human skin is neurogenic in origin and that it is in part mediated by the local release of nitric oxide. There appears to be little evidence for the involvement of mast cell-derived histamine in the initiation or modulation of ET-induced vasodilatation, in vivo. [source] Effect of intermittent compression of upper arm veins on forearm vessels in patients with end-stage renal diseaseHEMODIALYSIS INTERNATIONAL, Issue 3 2005Rina R. Rus Abstract Native arteriovenous fistula is the best vascular access for chronic hemodialysis. Primary and long-term success depends, in part, on the state of arteries and veins at the time of the operation. The aim of our study was to investigate the effects of intermittent compression of upper arm veins on forearm vessels in patients with terminal renal disease. The study group was composed of 16 chronic hemodialysis patients who performed daily intermittent compression of the upper arm without vascular access by elastic band (Eschmarch). Ten chronic hemodialysis patients were included in the control group, which performed no specific activity. Forearm measurements were obtained at the beginning of the study and 4 and 8 weeks later during the course of intermittent compression of the upper arm veins. The forearm circumference and maximal handgrip strength were measured. The artery measures, including endothelium-dependent vasodilatation and forearm vein variables, were obtained by ultrasonography measurements. The forearm circumference, maximal handgrip strength, and artery variables, including endothelium-dependent vasodilatation, remained unchanged. The basal venous diameters (2.29 ± 0.19 mm at the beginning, 2.46 ± 0.19 mm after 4 weeks, and 2.53 ± 0.18 mm after 8 weeks) were significantly increased in the study group. The distensibility of veins was preserved in the study group. There were no significant changes in the control group. Our study demonstrated that daily intermittent compression of the upper arm veins increases the forearm vein diameter and preserves the distensibility of veins in patients with end-stage renal failure. [source] Acute kidney injury in cirrhosis,HEPATOLOGY, Issue 6 2008Guadalupe Garcia-Tsao Acute renal failure (ARF), recently renamed acute kidney injury (AKI), is a relatively frequent problem, occurring in approximately 20% of hospitalized patients with cirrhosis. Although serum creatinine may underestimate the degree of renal dysfunction in cirrhosis, measures to diagnose and treat AKI should be made in patients in whom serum creatinine rises abruptly by 0.3 mg/dL or more (,26.4 ,mol/L) or increases by 150% or more (1.5-fold) from baseline. The most common causes of ARF (the term is used interchangeably with AKI) in cirrhosis are prerenal azotemia (volume-responsive prerenal AKI), acute tubular necrosis, and hepatorenal syndrome (HRS), a functional type of prerenal AKI exclusive of cirrhosis that does not respond to volume repletion. Because of the progressive vasodilatory state of cirrhosis that leads to relative hypovolemia and decreased renal blood flow, patients with decompensated cirrhosis are very susceptible to developing AKI with events associated with a decrease in effective arterial blood volume. HRS can occur spontaneously but is more frequently precipitated by events that worsen vasodilatation, such as spontaneous bacterial peritonitis. Conclusion: Specific therapies of AKI depend on the most likely cause and mechanism. Vasoconstrictors are useful bridging therapies in HRS. Ultimately, liver transplantation is indicated in otherwise reasonable candidates in whom AKI does not resolve with specific therapy. (HEPATOLOGY 2008;48:2064-2077.) [source] Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome,HEPATOLOGY, Issue 6 2007Aleksander Krag Patients with advanced cirrhosis and ascites are characterized by circulatory dysfunction with splanchnic vasodilatation and renal vasoconstriction, which often lead to ascites. The vasoconstrictor terlipressin improves renal function in hepatorenal syndrome (HRS). The aim of this study was to evaluate if terlipressin also improves renal function in patients with ascites without HRS. Twenty-three patients with cirrhosis participated; 15 with nonrefractory ascites were randomized to either terlipressin (N group, n = 11) or a placebo (P group, n = 4), and 8 had refractory ascites and received terlipressin (R group). The glomerular filtration rate (GFR), sodium clearance (CNa), lithium clearance (CLi), osmolal clearance (COsm), and urine sodium concentration (UNa) were assessed before and after the injection of 2 mg of terlipressin or the placebo. GFR increased in the N group (69 ± 19 versus 92 ± 25 mL/min, P < 0.005) and in the R group (31 ± 19 versus 41 ± 31 mL/min, P < 0.05) after terlipressin. In the N group, terlipressin induced an increase in CNa (0.89 ± 0.21 versus 1.52 ± 1.45 mL/min, P < 0.05), CLi (17.3 ± 8.9 versus 21.5 ± 11.6 mL/min, P < 0.05), and COsm (2.10 ± 0.81 versus 3.06 ± 2.0 mL/min, P < 0.05). In the R group, terlipressin induced an increase in CNa (0.11 ± 0.18 versus 0.35 ± 0.40 mL/min, P < 0.05) and CLi (5.5 ± 4.2 versus 9.5 ± 8.55 mL/min, P < 0.05). UNa increased in both groups after terlipressin (P < 0.005). Plasma norepinephrine (P < 0.05) and renin (P < 0.05) decreased after terlipressin. All parameters remained unchanged after the placebo. Conclusion: The vasopressin 1 receptor agonist terlipressin improves renal function and induces natriuresis in patients with cirrhosis and ascites without HRS. Vasoconstrictors may represent a novel future treatment modality for these patients. (HEPATOLOGY 2007.) [source] Functional significance of hepatic arterial flow reserve in patients with cirrhosisHEPATOLOGY, Issue 2 2003Alexander Zipprich In cirrhosis, hepatic arterial vasodilatation occurs in response to reduced portal venous blood flow. However, although the hepatic arterial flow reserve is high in patients with cirrhosis, its impact on hepatic function is unknown. This study investigated the effect of adenosine-induced hepatic arterial vasodilatation on different markers of liver function. In 20 patients with cirrhosis (Child-Pugh class A/B/C: n = 2/7/11) adenosine (2-30 ,g · min,1 · kg body wt,1) was infused into the hepatic artery and hepatic arterial average peak flow velocities (APV), pulsatility indices (PI), and blood flow volumes (HABF) were measured using digital angiography and intravascular Doppler sonography. Indocyanine green (ICG), lidocaine, and galactose were administered intravenously in doses of 0.5, 1.0, and 500 mg/kg body weight in the presence of adenosine-induced hepatic arterial vasodilatation and, on a separate study day, without adenosine. ICG disappearance, galactose elimination capacity (GEC), and formation of the lidocaine metabolite monoethylglycinxylidide (MEGX) were assessed. Adenosine markedly increased APV and HABF and markedly decreased PI. Serum MEGX concentrations were 63.7 ± 18.2 (median, 62; range, 36-107) and 99.0 ± 46.3 (82.5; 49-198) ng/mL in the absence and presence of adenosine infusion, respectively (P = .001). Adenosine-induced changes in MEGX concentrations were correlated inversely to changes in APV (r = ,0.5, P = .02) and PI (r = ,0.55, P = .01) and were more marked in Child-Pugh class C compared with Child-Pugh class A patients (57.4 ± 49.9 [44; ,14 to 140] vs. 8.4 ± 16.5 [13; ,11 to 35] ng/mL, P < .01). In conclusion, hepatic arterial vasodilatation provides substantial functional benefit in patients with cirrhosis. The effect does not depend directly on hepatic arterial macroperfusion and is observed preferentially in patients with decompensated disease. [source] Assessment of endothelial function as a marker of cardiovascular risk in patients with rheumatoid arthritisINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2010Faisel KHAN Abstract The endothelium is a major regulator of cardiovascular function and maintains an atheroprotective role through several mechanisms, including vasodilatation, inhibition of platelet aggregation, having anticoagulant and profibrinolytic effects, and having an anti-inflammatory effect. Early changes in the normal functioning of the endothelium are key initiating factors in the development and progression of atherosclerosis. These changes are present well before the presentation of clinical symptoms. Thus, researchers have focused much attention on developing methods for reliable non-invasive testing of endothelial function to allow early detection and monitoring and progression of subclinical atherosclerosis. To date, there is a wide range of methods in use to assess endothelial function, each with its own advantages and limitations. Ideally, the tests should be non-invasive to allow repeated measurements and be applicable in normal healthy subjects and also in children. Given the wide range of regulatory functions of the endothelium, it is not surprising that there is no single measure of endothelial function that provides all the necessary information regarding vascular integrity in different vascular beds. Therefore, a combination of tests examining different components of the vascular system is more appropriate. Since patients with rheumatoid arthritis have increased mortality due to cardiovascular disease, assessment of endothelial function could prove to be useful tools in the identification and monitoring of cardiovascular risk. The purpose of this review is to give a brief overview of some of the commonly used techniques for assessment of endothelial function, and in particular on those that have been used in studies of patients with rheumatoid arthritis. [source] Paradoxical Vasodilation During Lower Body Negative Pressure in Patients with Vasodepressor Carotid Sinus SyndromeJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2003Arduino A. Mangoni MD OBJECTIVES: To elucidate the pathophysiological mechanism of the vasodepressor form (VD) of carotid sinus syndrome (CSS) by maneuvers designed to induce generalized sympathetic activation after baroreceptor unloading (lower body negative pressure, LBNP) or direct peripheral adrenoreceptor stimulation via local administration of norepinephrine (NA). DESIGN: Subjects were identified with VD of CSS through diagnostic testing. SETTING: Research laboratory. PARTICIPANTS: Eleven young controls (YC) (mean age ± standard error of mean = 22.8 ± 0.7), eight elderly controls (EC) (72.6 ± 0.6), and eight elderly patients with VD (78.7 ± 1.7). MEASUREMENTS: Forearm arterial blood flow (FABF) was measured in the left and right arms by venous occlusion plethysmography. Measurements were performed during baseline conditions, LBNP (,20 mmHg), and intra-arterial NA infusion in the left brachial artery at three progressively increasing rates (60, 120, and 240 pmol/min). RESULTS: During LBNP, FABF significantly decreased in YC (baseline 3.61 ± 0.30 vs ,20 mmHg 2.96 ± 0.24 mL/100 g/min, P = .030) and EC (4.05 ± 0.74 vs 3.69 ± 0.65 mL/100 g/min, P = .033) but increased in elderly patients with VD (3.65 ± 0.60 vs 4.54 ± 0.80 mL/100 g/min, P = .020). During NA infusion, a significant forearm vasoconstriction occurred in YC (FABF left:right ratio 1.00 ± 0.05 at baseline; 0.81 ± 0.08 at 60 pmol/min, P = .034; 0.81 ± 0.05 at 120 pmol/min, P < .001; 0.72 ± 0.04 at 240 pmol/min, P < .001), whereas no significant FABF changes were observed in EC (1.04 ± 0.06; 0.96 ± 0.07, P = .655; 0.89 ± 0.10, P = .401; 0.94 ± 0.10, P = .590) or elderly patients with VD (1.04 ± 0.06; 1.16 ±0 .10, P = .117; 1.04 ± 0.08, P = .602; 1.11 ± 0.10, P = .305). CONCLUSION: VD of CSS is associated with a paradoxical vasodilatation during LBNP and an impairment of peripheral ,-adrenergic responsiveness, which may be age-related. [source] Role of Endothelium/Nitric Oxide and Cyclic AMP in Isoproterenol Potentiation of 17ß-Estradiol-Mediated VasorelaxationJOURNAL OF CARDIAC SURGERY, Issue 6 2002HY Chan Estrogen exerts vasorelaxation and cardiac protection via multiple cellular mechanisms. Estrogen modifies vasodilatation induced by certain relaxants such as ß-adrenoceptor agonists. However, little is known whether low concentrations of ß-adrenoceptor agonists would also influence the acute relaxant response to estrogen. The present study was designed to investigate the synergistic interaction between isoproterenol and 17ß-estradiol, and to study the role of endothelium and cyclic AMP-dependent pathway in this interaction. Changes in vessel tone of the isolated rat mesenteric artery rings were measured by force-displacement Grass transducer. In 9,11-dideoxy-11,, 9,-epoxy-methanoprostaglandin F2, - preconstricted endothelium-intact rings, 17ß-estradiol induced concentration-dependent relaxation with pD2 of 5.074 ± 0.043. Pretreatment of endothelium-intact rings with isoproterenol (1-3 × 10 -9 M, 1-h incubation time) significantly enhanced 17,-estradiol-induced relaxation. Longer incubation (2.5 h) did not produce further amplifying effect. This effect was inhibited by Rp-cGMPS triethylamine (3 × 10 -6 M), and disappeared in the presence of 3 × 10 -5 M NG -nitro-L-arginine methyl ester or in the endothelium-denuded rings. The effect of isoproterenol was partially antagonized by propranolol (3 × 10 -6 M), ICI 118,551 (3 × 10 -6 M) but not by atenolol (10 -5 M). None of three ,-adrenoceptor antagonists affected 17ß-estradiol-induced relaxation in the absence of isoproterenol. Rp-cAMPS triethylamine (3 × 10 -6 M) abolished the effect of isoproterenol. Besides, exposure to 3 × 10 -9 M forskolin for 1 h also potentiated the relaxant response to 17,-estradiol. In summary, this isoproterenol enhancement was dependent on the presence of endothelium and abolished by L-NAME via a ,2 -adrenoceptor-mediated cyclic AMP-dependent mechanism. These data also indicate the possible existence of cyclic AMP-dependent nitric oxide-producing pathway in the regulation of the vascular response to vasodilators. (supported by UPGC Direct Grant) [source] Pulse oximeter perfusion index as an early indicator of sympathectomy after epidural anesthesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009Y. GINOSAR Background: The pulse oximeter perfusion index (PI) has been used to indicate sympathectomy-induced vasodilatation. We hypothesized that pulse oximeter PI provides an earlier and clearer indication of sympathectomy following epidural anesthesia than skin temperature and arterial pressure. Methods: Forty patients received lumbar epidural catheters. Patients were randomized to receive either 10 ml 0.5% bupivacaine or 10 ml 0.25% bupivacaine. PI in the toe, mean arterial pressure (MAP) and toe temperature were all assessed at baseline and at 5, 10 and 20 min following epidural anesthesia. The effect of epidural anesthesia over time was assessed by repeated measures analysis of variance. Additionally, we defined clinically evident sympathectomy criteria (a 100% increase in the PI, a 15% decrease in MAP and a 1 °C increase in toe temperature). The numbers of patients demonstrating these changes for each test were compared using the McNemar test for each time point. Results: Twenty-nine subjects had photoplethysmography signals that met a priori signal quality criteria for analysis. By 20 min, PI increased by 326%, compared with a 10% decrease and a 3% increase in MAP and toe temperature, respectively. For PI 15/29, 26/29 and 29/29 of the subjects met the sympathectomy criteria at 5, 10 and 20 min, respectively, compared with 4/29, 6/29 and 18/29 for MAP changes and 3/29, 8/29 and 14/29 for toe temperature changes. Conclusions: PI was an earlier, clearer and more sensitive indicator of the development of epidural-induced sympathectomy than either skin temperature or MAP. [source] Induction of oxidative stress by homocyst(e)ine impairs endothelial function,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2001Vibhas S. Mujumdar Abstract Previous studies have demonstrated a relationship between hyperhomocysteinemia and endothelial dysfunction, reduced bioavailability of nitric oxide, elastinolysis and, vascular muscle cell proliferation. In vivo decreased nitric oxide production is associated with increased matrix metalloproteinase (MMP) activity and formation of nitrotyrosine. To test the hypothesis that homocysteine neutralizes vascular endothelial nitric oxide, activates metalloproteinase, causes elastinolysis and vascular hypertrophy, we isolated aortas from normotensive Wistar rats and cultured them in medium containing homocysteine, and calf serum for 14 days. Homocysteine-mediated impairment of endothelial-dependent vasodilatation was reversed by co-incubation of homocysteine with nicotinamide (an inhibitor of peroxinitrite and nitrotyrosine), suggesting a role of homocysteine in redox-mediating endothelial dysfunction and nitrotyrosine formation. The Western blot analysis, using anti-nitrotyrosine antibody, on aortic tissue homogeneates demonstrated decreased nitrotyrosine in hyperhomocysteinemic vessels treated with nicotinamide. Zymographic analysis revealed increased elastinolytic gelatinase A and B (MMP-2, -9) in homocysteine treated vessels and the treatment with nicotinamide decreases the homocysteine-induced MMP activation. Morphometric analyses revealed significant medial hypertrophic thickening (1.4,±,0.2-fold of control, P,=,0.03) and elastin disruption in homocysteine-treated vessels as compared to control. To determine whether homocysteine causes endothelial cell injury, cross-sections of aortas were analyzed for caspase activity by incubating with Ac-YVAD-AMC (substrate for apoptotic enzyme, caspase). The endothelium of homocysteine treated vessels, and endothelial cells treated with homocysteine, showed marked labeling for caspase. The length-tension relationship of homocysteine treated aortas was shifted to the left as compared to untreated aortas, indicating reduced vascular elastic compliance in homocysteine-treated vessels. Co-incubation of homocysteine and inhibitors of MMP, tissue inhibitor of metalloproteinase-4 (TIMP-4), and caspase, YVAD-CHO, improved vascular function. The results suggest that alteration in vascular elastin/collagen ratio and activation of MMP-2 are associated with decreased NO production in hyperhomocysteinemia. J. Cell. Biochem. 82:491,500, 2001. © 2001 Wiley-Liss, Inc. [source] Evaluation of metalloproteinases 2 and 9 and their inhibitors in physiologic and pre-eclamptic pregnancyJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2009Martina Montagnana Abstract Matrix metalloproteinases (MMPs) are a family of zinc and calcium-dependent endopeptidases involved in remodeling and physiological homeostasis of extracellular matrix (ECM). The metalloproteinases activity is predominantly modulated by specific tissue inhibitors of matrix metalloproteinases (TIMPs). The balance between MMPs and TIMPs is likely to play an important role in remodeling uterine arteries in pregnancy, and it may represent means by which vasodilatation is maintained in later pregnancy. Moreover, increased levels of MMPs and in particular MMP-2 play a role in the vascular alterations induced by hypertension. The aim of this study was the evaluation of MMP-2 and -9, along with their inhibitors TIMP-1 and -2, in pre-eclamptic women compared with normotensive pregnancy and non-pregnant women. Fourteen pre-eclamptic women were compared with 37 normotensive women in different gestational age and 21 non-pregnant women. Multiplexed sandwich enzyme-linked immunosorbent assay was used to measure MMPs and TIMPs simultaneously. MMP-2 levels were significantly higher in pre-eclamptic women vs. both non-pregnant and physiologic pregnant women. MMP-9 concentrations were significantly higher in physiologic pregnant vs. non-pregnant women. The serum levels of TIMP-1 were significantly higher in pre-eclamptic vs. both non-pregnant and physiologic pregnant women. TIMP-2 values were higher in physiologic pregnant women and pre-eclamptic women vs. non-pregnant women. A positive correlation between MMP-9 values and gestational age was observed in normal pregnant women. Results of the present investigation confirm that MMP-2 and TIMP-1 values are significantly higher in preeclampsia. We confirm that the modification of the fine balance between MMPs and their inhibitors plays a greater role in the structural and functional vascular changes of women with complicated pregnancies. J. Clin. Lab. Anal. 23:88,92, 2009. © 2009 Wiley-Liss, Inc. [source] Changes in renal artery resistance after meal-induced splanchnic vasodilatation in cirrhotic patientsJOURNAL OF CLINICAL ULTRASOUND, Issue 9 2001Pascal Perney MD Abstract Purpose A relationship between vasomotor tone changes in mesenteric and renal vessels in cirrhotic patients has been suspected but remains controversial. The aim of this study was to assess by duplex Doppler sonography the changes in the circulatory resistance of the renal arteries and superior mesenteric artery (SMA) following meal-induced splanchnic vasodilatation. Methods Twenty-seven cirrhotic patients and 15 healthy volunteers with no hepatic or renal dysfunction were prospectively included in the study. The resistance index (RI) of the SMA and of the right and left renal arteries was measured by duplex Doppler sonography before and 30 minutes after ingestion of a standard 400-kcal balanced liquid meal. Values in controls and patients and values before and after the meal were compared, and correlations between RIs, Child-Pugh class (liver function), and creatinine clearance were assessed in cirrhotic patients. Results The fasting renal artery RI was greater in cirrhotic patients than in controls (p < 0.0001), but there was no difference in fasting SMA RIs. After the meal, there was a significant decrease in the SMA RI in controls (0.85 ± 0.04 before versus 0.74 ± 0.03 after meal, p = 0.0001) and in cirrhotic patients (0.85 ± 0.04 before versus 0.77 ± 0.04 after, p = 0.0001) and a significant increase in the renal artery RI (0.57 ± 0.06 before versus 0.62 ± 0.05 after in controls, p = 0.001; 0.68 ± 0.07 before versus 0.70 ± 0.07 after in cirrhotic patients, p = 0.001). No correlation was found in cirrhotic patients between the changes in renal artery RI and the postprandial SMA RI decrease, the Child-Pugh class, or the creatinine clearance. Conclusions Meal-induced SMA vasodilatation (RI decrease) is associated with a marked increase in the renal artery RI, worsening the renal vasoconstriction in cirrhotic patients. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:506,512, 2001. [source] Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammationAGING CELL, Issue 3 2009Leocadio Rodríguez-Mañas Summary Vascular endothelial dysfunction occurs during the human aging process, and it is considered as a crucial event in the development of many vasculopathies. We investigated the underlying mechanisms of this process, particularly those related with oxidative stress and inflammation, in the vasculature of subjects aged 18,91 years without cardiovascular disease or risk factors. In isolated mesenteric microvessels from these subjects, an age-dependent impairment of the endothelium-dependent relaxations to bradykinin was observed. Similar results were observed by plethysmography in the forearm blood flow in response to acetylcholine. In microvessels from subjects aged less than 60 years, most of the bradykinin-induced relaxation was due to nitric oxide release while the rest was sensitive to cyclooxygenase (COX) blockade. In microvessels from subjects older than 60 years, this COX-derived vasodilatation was lost but a COX-derived vasoconstriction occurred. Evidence for age-related vascular oxidant and inflammatory environment was observed, which could be related to the development of endothelial dysfunction. Indeed, aged microvessels showed superoxide anions (O2,) and peroxynitrite (ONOO,) formation, enhancement of NADPH oxidase and inducible NO synthase expression. Pharmacological interference of COX, thromboxane A2/prostaglandin H2 receptor, O2,, ONOO,, inducible NO synthase, and NADPH oxidase improved the age-related endothelial dysfunction. In situ vascular nuclear factor-,B activation was enhanced with age, which correlated with endothelial dysfunction. We conclude that the age-dependent endothelial dysfunction in human vessels is due to the combined effect of oxidative stress and vascular wall inflammation. [source] | |||||||||||||||||||||||||||||||||||||