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Vascular Beds (vascular + bed)
Kinds of Vascular Beds Selected AbstractsMuscle metaboreflex control of the circulation during exerciseACTA PHYSIOLOGICA, Issue 4 2010R. Boushel Abstract This review covers the control of blood pressure, cardiac output and muscle blood flow by the muscle metaboreflex which involves chemically sensitive nerves located in muscle parenchyma activated by metabolites accumulating in the muscle during contraction. The efferent response to metaboreflex activation is an increase in sympathetic nerve activity that constricts the systemic vasculature and also evokes parallel inotropic and chronotropic effects on the heart to increase cardiac output. The metaboreflex elicits a significant blood pressure elevating response during exercise and functions to redistribute blood flow and blood volume. Regional specificity in the efferent response to the metaboreflex activated from either the leg or the arm is seen in the balance between signals for vasoconstriction to curtail blood flow and signals to increase cardiac output. The metaboreflex has dual functions. It can both elevate and decrease muscle blood flow depending on (1) the intensity and mode of contraction, (2) the limb in which the reflex is evoked, (3) the strength of the signal defined by the muscle mass, (4) the extent to which blood flow is redistributed from inactive vascular beds to increase central blood volume and (5) the extent to which cardiac output can be increased. [source] Endothelium-specific Cre recombinase activity in flk-1-Cre transgenic miceDEVELOPMENTAL DYNAMICS, Issue 2 2004Alexander H. Licht Abstract The use of the Cre-loxP recombination system allows the conditional inactivation of genes in mice. The availability of transgenic mice in which the Cre recombinase expression is highly cell type specific is a prerequisite to successfully use this system. We previously have characterized regulatory regions of the mouse flk-1 gene sufficient for endothelial cell-specific expression of the LacZ reporter gene in transgenic mice. These regions were fused to the Cre recombinase gene, and transgenic mouse lines were generated. In the resulting flk-1-Cre transgenic mice, specificity of Cre activity was determined by cross-breeding with the reporter mouse lines Rosa26R or CAG-CAT-LacZ. We examined double-transgenic mice at different stages of embryonic development (E9.5,E16.5) and organs of adult animals by LacZ staining. Strong endothelium-specific staining of most vascular beds was observed in embryos older than E11.5 in one or E13.5 in a second line. In addition, the neovasculature of experimental BFS-1 tumors expressed the transgene. These lines will be valuable for the conditional inactivation of floxed target genes in endothelial cells of the embryonic vascular system. Developmental Dynamics 229:312,318, 2004. © 2004 Wiley-Liss, Inc. [source] Vascular effects of adenosine and its analoguesDRUG DEVELOPMENT RESEARCH, Issue 1-2 2001Debbie Prentice Abstract The main action of adenosine on vascular beds is vasodilation via A2 receptors. In addition, A1 receptors are found in some blood vessels, where they cause contraction. Traditionally, adenosine-induced vasodilation in vitro has been attributed to A2A receptor activation; however, it is now clear that A2B receptors are also involved in the regulation of vascular tone. Endothelium dependence of A2 receptor-mediated responses is variable; in some tissues they are blocked by removal of endothelium and/or inhibition of NO-synthase and in some they are not. In addition to A2 receptor-mediated relaxation, there is much evidence that relaxations to adenosine and some of its analogues can also be mediated by a mechanism which cannot be blocked by adenosine receptor antagonists. There is evidence that these responses are endothelium- and NO-independent and that, under conditions where adenosine is taken up into cells, relaxations to the endogenous ligand are entirely mediated by this mechanism, suggesting it is of physiological significance. Drug Dev. Res. 52:346,349, 2001. © 2001 Wiley-Liss, Inc. [source] Vasodilator Stress Induces Infrequent Wall Thickening Abnormalities Compared to Perfusion Defects in Mild-to-Moderate Coronary Artery Disease: Implications for the Choice of Imaging Modality with Vasodilator StressECHOCARDIOGRAPHY, Issue 4 2004M.R.C.P., Ph.D., Prem Soman M.D. Background: Experimental evidence suggests that although vasodilator stress agents consistently induce regional flow disparity between stenosed and normal coronary vascular beds, the occurrence of functional myocardial ischemia is infrequent, especially in mild-to-moderate coronary artery stenosis. Thus, it is hypothesized that dipyridamole infusion, even at high doses, will result in a disproportionately higher frequency of perfusion defects compared to regional wall thickening abnormalities. Methods: We performed simultaneous high-dose (0.84 mg/kg) dipyridamole stress echocardiography (Echo) and Tc-99m sestamibi SPECT (MIBI, methoxyisobutyl isonitrile) in 46 patients with coronary artery diameter stenosis >50% and ,90% in one or two epicardial coronary arteries, and no previous myocardial infarction. Results: Of a total of 828 segments, MIBI showed 97 reversible defects while Echo showed only 23 reversible wall thickening abnormalities. Of the 97 segments with reversible MIBI defects, only 13 (13%) showed simultaneous reversible wall thickening abnormalities during dipyridamole infusion. There were 24 patients with MIBI defects, of whom 10 (41%) showed a corresponding wall thickening abnormality. The sensitivity of MIBI and Echo for the detection of coronary artery disease was 52% and 21%, respectively (P = 0.001). Conclusion: This suggests that vasodilator stress is not optimally suited for use with techniques that use regional wall thickening abnormality as a marker of ischemia for the diagnosis of coronary artery disease. (ECHOCARDIOGRAPHY, Volume 21, May 2004) [source] Arterial Myogenic Properties of the Spontaneously Hypertensive RatEXPERIMENTAL PHYSIOLOGY, Issue 5 2002Jennifer M. Hughes When subject to a transmural pressure gradient resistance arteries develop a spontaneous, intrinsically initiated contraction which varies according to the pressure stimulus and occurs in the absence of vasoconstrictor agonists. Such pressure-dependent active changes in vascular tone are indicative of the vascular myogenic response and contribute to autoregulation and the setting of total peripheral resistance and hence blood pressure regulation. The myogenic behaviour of blood vessels provides the background tone upon which other vasomotor influences act. Hypertension is associated with a raised vascular resistance and in this article the evidence for increased myogenic activity contributing to the raised vascular resistance is reviewed. Although there are some cases that provide evidence for exaggerated myogenic responsiveness in resistance arteries taken from hypertensive animals it is not possible to conclude that enhanced myogenic contractile responses within normal pressure ranges contribute to the raised total peripheral resistance. However, the myogenic tone of the resistance arteries of the various vascular beds is subject to differing modulatory influences in hypertensive animals and their normotensive controls which may contribute to the aetiology of hypertension. [source] Possible Contribution of Central Gamma-Aminobutyric Acid Receptors to Resting Vascular Tone in Freely Moving RatsEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Yumi Takemoto Previous studies have shown that central administration of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, preferentially reduces hindquarters and carotid vascular resistances but not renal and coeliac vascular resistances in conscious rats. This study tested the hypothesis that these preferential actions of central GABA receptors are related to differences between vessels in resting autonomic vascular tone in freely moving rats. Rats were chronically implanted with intracisternal cannulas and/or electromagnetic probes to measure regional blood flows. In response to GABA administration, the changes in vascular resistance (arterial blood pressure/regional blood flow) of the hindquarters (n = 23) and carotid (n = 12) vascular beds were significantly and negatively correlated with basal vascular resistance. No such relationship was found for the renal (n = 21), coeliac (n = 13) and superior mesenteric (n = 23) vascular beds. This finding indicates that the responsiveness to GABA of brainstem pathways controlling the hindquarters and carotid vascular beds co-varies with resting resistance in hindquarters and carotid vessels. A similar analysis was performed, correlating the ongoing vascular resistance of each vessel with its response to ganglionic blockade by chlorisondamine. In this case, a significant negative correlation was also found for the hindquarters (n = 26) and carotid (n = 15) vascular beds, but not for the coeliac (n = 17) or superior mesenteric (n = 19) vessels. Together, these findings suggest that central GABA receptors accessible from the cisterna magna preferentially affect two vascular beds which, in the freely moving rat, show resting autonomic vascular tone. [source] Contribution of endothelium-derived hyperpolarizing factors to the regulation of vascular tone in humansFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2008Jeremy Bellien Abstract Endothelium plays a crucial role in the regulation of cardiovascular homeostasis through the release of vasoactive factors. Besides nitric oxide (NO) and prostacyclin, increasing evidences show that endothelium-derived hyperpolarizing factors (EDHF) participate in the control of vasomotor tone through the activation of calcium-activated potassium channels. In humans, the role of EDHF has been demonstrated in various vascular beds including coronary, peripheral, skin and venous vessels. The mechanisms of EDHF-type relaxations identified in humans involved the release by the endothelium of hydrogen peroxide, epoxyeicosatrienoic acids (EETs), potassium ions and electronical communication through the gap junctions. The role of EETs could be particularly important because, in addition contributing to the maintenance of the basal tone and endothelium-dependent dilation of conduit arteries, these factors share many vascular protective properties of NO. The alteration of which might be involved in the physiopathology of cardiovascular diseases. The evolution of EDHF availability in human pathology is currently under investigation with some results demonstrating an increase in EDHF release to compensate the loss of NO synthesis and to maintain the endothelial vasomotor function whereas others reported a parallel decrease in NO and EDHF-mediated relaxations. Thus, the modulation of EDHF activity emerges as a new pharmacological target and some existing therapies in particular those affecting the renin,angiotensin system have already been shown to improve endothelial function through hyperpolarizing mechanisms. In this context, the development of new specific pharmacological agents especially those increasing EETs availability may help to prevent endothelial dysfunction and therefore enhance cardiovascular protection in patients. [source] Cardiovascular pharmacology and physiology of the isoprostanesFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2006Jean-Luc Cracowski Abstract F2 -isoprostanes are a complex family of compounds produced from arachidonic acid via a free radical-catalyzed mechanism. Their quantification as a pathophysiological biomarker provides a unique opportunity to investigate lipid peroxidation in vascular diseases. Their measurement also provides an interesting biomarker for the rational dose selection of antioxidants in vascular diseases where oxidative stress might be involved. In addition to their use as biomarkers, some isoprostanes possess a biological activity. The 15-series F2 - and E2 -isoprostanes mediate vasoconstriction in different vascular beds and species. In addition, 15-F2t -IsoP induces smooth muscle cells mitogenesis and monocyte adhesion to endothelial cells. The data available supports but does not prove the hypothesis that isoprostanes are involved in vascular physiology and pathogenesis. [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] Simvastatin effects on portal-systemic collaterals of portal hypertensive ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2010Hui-Chun Huang Abstract Background and Aim:, Portal-systemic collateral vascular resistance and vasoconstrictor responsiveness are crucial in portal hypertension and variceal bleeding control. Statins enhance vasodilators production, but their influence on collaterals is unknown. This study aimed to survey the effect of simvastatin on collaterals. Methods:, Partially portal vein-ligated rats received oral simvastatin (20 mg/kg/day) or distilled water from ,2 to +7 day of ligation. After hemodynamic measurements on the eighth postoperative day, baseline perfusion pressure (i.e. an index of collateral vascular resistance) and arginine vasopressin (AVP, 0.1 nM,0.1 µM) responsiveness were evaluated with an in situ perfusion model for collateral vascular beds. RT-PCR of endothelial NO synthase (eNOS), inducible NOS (iNOS), cyclooxygenase-1 (COX-1), COX-2, thromboxane A2 synthase (TXA2 -S) and prostacyclin synthase genes was performed in parallel groups for splenorenal shunt (SRS), the most prominent intra-abdominal collateral vessel. To determine the acute effects of simvastatin, collateral AVP response was assessed with vehicle or simvastatin. SRS RT-PCR of eNOS, iNOS, COX-1, COX-2 and TXA2 -S, and measurements of perfusate nitrite/nitrate, 6-keto-PGF1, and TXB2 levels were performed in parallel groups without AVP. Results:, Acute simvastatin administration enhanced SRS eNOS expression and elevated perfusate nitrite/nitrate and 6-keto-PGF1, concentrations. Chronic simvastatin treatment reduced baseline collateral vascular resistance and portal pressure and enhanced SRS eNOS, COX-2 and TXA2 -S mRNA expression. Neither acute nor chronic simvastatin administration influenced collateral AVP responsiveness. Conclusion:, Simvastatin reduces portal-systemic collateral vascular resistance and portal pressure in portal hypertensive rats. This may be related to the enhanced portal-systemic collateral vascular NO and prostacyclin activities. [source] Combined tissue factor pathway inhibitor and thrombomodulin deficiency produces an augmented hypercoagulable state with tissue-specific fibrin depositionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2008S. A. MARONEY Summary.,Background and Objective:,Tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) are endothelial-associated anticoagulant proteins thought to control hemostasis in specific vascular beds. Here, we have examined the consequences of TFPI deficiency in the presence of a compounding procoagulant state caused by reduced TM function. Methods and results:,TFPI+/,/TMpro/pro mice are born at less than expected frequency in either TFPI+/,/TMpro/+ or TMpro/pro mothers but are born at near the expected frequency in TMpro/+ mothers. Adult TFPI+/,/TMpro/pro mice have elevated thrombin,antithrombin complex and increased thrombus volume in an electrical injury model of venous thrombosis. In striking contrast to mice with single deficiency of TFPI or TM, TFPI+/,/TMpro/pro mice exhibit augmented fibrin deposition not only in the liver, but also in the cerebral microvasculature. Conclusions:,TFPI+/,/TMpro/pro mice exhibit partial intrauterine lethality when carried by mothers with an underlying prothrombotic state, providing the first experimental evidence in an animal model that TFPI-dependent control of hemostasis in the vascular bed of the placenta fulfills a critical role for successful pregnancy outcome. In addition to the placenta, partial TFPI deficiency interacts with decreased TM function in an organ selective manner to produce fibrin deposition in other specific vascular beds, the liver and brain. [source] Regulation of Endothelial Cell Adhesion Molecule Expression in an Experimental Model of Cerebral MalariaMICROCIRCULATION, Issue 6 2002PHILLIPE R. BAUER ABSTRACT Objective: Plasmodium falciparum malaria in humans and animal models of this disease have revealed changes in the infected host that are consistent with a systemic inflammatory response. Although it has been proposed that endothelial cell adhesion molecules (CAM) contribute to the adhesive interactions of Plasmodium -infected erythrocytes and immune cells with vascular endothelial cells, ECAM expression has not been systematically studied in Plasmodium -infected animals. Methods: In this study, the dual radiolabeled monoclonal antibody method was used to quantify the expression of different ECAMs (ICAM-1, VCAM-1, P-selectin, E-selectin) in different regional vascular beds of Plasmodium berghei ANKA-inffected mice (PbA), a well-recognized model of human cerebral malaria. The roles of T lymphocytes and certain cytokines (TNF-,, IL-12, IFN-,) in mediating the infection-induced expression of ICAM-1 and P-selectin were assessed by using relevant mutant mice. Results: Wild-type (WT) mice exhibited highly significant increases in the expression of ICAM-1, VCAM-1, and P-selectin (but not E-selectin) in all vascular beds on the 6th day of PbA infection. The PbA -induced upregulation of ICAM-1 was significantly blunted in mice that were either deficient in IFN-,, IL-12 (but not TNF1b) or T lymphocytes (Rag-1 deficiency); however, these responses were tissue specific. Conclusions: These findings indicate that vascular endothelial cells in most regional circulations assume an inflammatory phenotype and that cytokines and immune cells mediate this response in a tissue-specific manner. [source] Attenuation of Histamine-Induced Endothelial Permeability Responses after Pacing-Induced Heart Failure: Role for Endogenous CatecholaminesMICROCIRCULATION, Issue 5 2000DONNA L. DYESS ABSTRACT Objective: After congestive heart failure (CHF), lung endothelial permeability responses to a number of perturbations, including acute barotrauma, angiotensin II, and thapsigargin are blunted. Our hypothesis was that similar attenuation of permeability responses occurs in peripheral vascular beds after CHF. We compared peripheral microvascular permeability responses to the autacoid histamine in control dogs and in dogs paced to heart failure (245 bpm for ,36 days). Since catecholamines attenuate autacoid-induced increases in microvascular permeability in skin and muscle in normal animals, we also tested whether the known elevation in catecholamines in CHF was involved in any downregulation of permeability responses in this group. Methods: Control and paced dogs were anesthetized, intubated, and ventilated, and a hindpaw lymphatic cannulated. The reflection coefficient for total proteins (,) was measured at baseline and during one-hour, local intra-arterial histamine infusion. Results: In controls, , fell from 0.83 ± 0.02 to 0.73 ± 0.04 after histamine (p < 0.05), while in the paced group , was no different from that at baseline (0.77 ± 0.02). To test whether this difference was due to endogenous catecholamines, dogs were pretreated with propranolol (controls only) or the specific ,2 -antagonist ICI 118,551 prior to histamine infusion. After ,-blockade, histamine significantly reduced , in both control (0.83 ± 0.01 to 0.55 ± 0.05) and paced (0.83 ± 0.01 to 0.57 ± 0.07) groups (p < 0.05). Conclusion: We conclude that endogenous catecholamines, acting via ,2 -adrenergic receptors, attenuate the permeability response to histamine in pacing-induced heart failure. [source] Expression of Endothelial Cell Adhesion Molecules in Neovascularized TissueMICROCIRCULATION, Issue 4 2000GINA VALLIEN ABSTRACT Objective: Recent studies indicate that endothelial cells of newly formed blood vessels are activated and exhibit a distinct phenotype that may influence the responses of these microvessels to an inflammatory stimulus. The objective of this study was to compare the basal and cytokine-stimulated expression of endothelial cell adhesion molecules in neovascularized tissue to normal (nonproliferating) vascular beds. Methods: The expression of P- and E-selectin, VCAM-1, ICAM-1, ICAM-2, and PECAM-1 was measured, using the dual radiolabeled mAb technique, in subcutaneously implanted (for 10,15 days) polyurethane sponges, skin, heart, lung, and intestine of male C57BL/6 mice (background). Results: Basal values of PECAM-1 and ICAM-2 revealed a low vascular density in the implanted sponge matrices that is comparable to skin. When normalized for vascular surface area (PECAM-1 or ICAM-1 expression), the basal level of E- and P-selectin expression was highest in neovascularized sponge and skin. TNF-, elicited an increased expression of all endothelial CAMs, except PECAM-1 and ICAM-2, but the responses were blunted in sponge and skin, relative to other vascular beds. Conclusions: These findings indicate that endothelial cells in newly formed blood vessels exhibit a pattern of basal and cytokine-induced expression of certain adhesion glycoproteins that is similar to nonproliferating cutaneous vessels. [source] Latest news and product developmentsPRESCRIBER, Issue 8 2007Article first published online: 23 JUL 200 Lamotrigine for partial, valproate for generalised A large UK trial has shown that lamotrigine is the most effective choice in the treatment of partial epilepsy (Lancet 2007;369: 1000-15). The SANAD trial, commissioned by the National Institute for Health Research's Health Technology Assessment programme, randomised 1721 patients (for whom carbamazepine monotherapy would have been the treatment of choice) to treatment with carbamazepine, gabapentin, lamotrigine, oxcarbazepine (Trileptal) or topiramate (Topamax). Lamotrigine was associated with a longer time to treatment failure, though time to 12-month remission favoured carbamazepine. Over four years' follow-up, lamotrigine was numerically but not significantly superior. The authors concluded lamotrigine is clinically superior to carbamazepine for partial epilepsy A second arm of the trial, yet to be published, evaluated the treatment of generalised epilepsy and found valproate to be clinically most effective, though topiramate was cost effective for some patients. Chronic pain common in nursing homes Most residents in nursing homes say they have long- term pain but only one in seven say a health professional has ever discussed its treatment with them, according to a report by the Patients' Association (www.patients-association.org.uk). Pain in Older People ,A Hidden Problem was a qualitative study of 77 older residents in care homes in England. Most were frail and suffered long-term illness. The study found that 85 per cent of residents said they were often troubled by aches or pains and these lasted over a year in 74 per cent. Most described their pain as moderate (33 per cent) or severe (38 per cent) but 8 per cent said it was excruciating. Many reported limitations on mobility and social activities despite a high level of stoicism. All but one were taking medication to relive pain; one-third experienced adverse effects but 78 per cent believed drugs offered the most effective treatment. One-quarter said a doctor or nurse had discussed how to stop their pain worsening, and 15 per cent said they had discussed how to treat their pain. Visits from GPs appeared to be uncommon. Atherothrombotic events despite treatment Between one in five and one in seven of high-risk patients experience atherothrombotic events despite evidence-based treatment, the REACH study has shown (J Am Med Assoc 2007;297:1197-1206). REACH (REduction of Atherothrombosis for Continued Health) is an international observational study involving 68 236 patients with atherothrombotic disease or at least three risk factors. Most were taking conventional evidence-based medication. After one year, the incidence of the combined endpoint of cardiovascular death, myocardial infarction, stroke or hospitalisation for atherothrombotic events was approximately 15 per cent for patients with coronary artery disease or cardiovascular disease, and 21 per cent in patients with peripheral artery disease and established coronary disease. Event rates increased with the number of vascular beds affected, rising to 26 per cent in patients with three symptomatic arterial disease locations. Extended CD prescribing by nurses and pharmacists The Medicines and Healthcare products Regulatory Agency (MHRA) is consulting on expanding the prescribing of controlled drugs (CDs) by nonmedical prescribers. Currently, nurse independent prescribers can prescribe 12 CDs, including diamorphine and morphine, but pharmacist independent prescribers may not prescribe any CDs. The proposal is to allow both professions to prescribe any CDs within their competence, with the exception of cocaine, diamorphine or dipipanone for the management of addiction. The closing date for consultation is 15 June. Consultation is also underway on expanding the range of CDs nurses and pharmacists can prescribe under a patient group direction (PGD), and their use for pain relief. The closing date for consultation is 20 April. Intrinsa: transdermal testosterone for women A transdermal formulation of testosterone has been introduced for the treatment of low sexual desire associated with distress in women who have experienced an early menopause following hysterectomy involving a bilateral oophorectomy and are receiving concomitant oestrogen therapy. Manufacturer Procter & Gamble says that Intrinsa, a twice-weekly patch, delivers testosterone 300µg every 24 hours, achieving premenopausal serum testosterone levels. Clinical trials showed that Intrinsa reduced distress in 65-68 per cent and increased satisfying sexual activity in 51-74 per cent of women. A month's treatment (eight patches) costs £28.00. Fish oil for secondary ,not primary ,prevention of CHD Supplementing statin therapy with eicosapentaenoic acid (EPA) reduces the risk of major coronary events in patients with coronary heart disease (CHD) ,but not in patients with no history of CHD Lancet 2007;369:1090-8). The five-year study in 18 645 patients with total cholesterol levels of 6.5mmol per litre or greater found that the incidence of sudden cardiac death, fatal and nonfatal myocardial infarction in CHD patients treated with EPA plus a statin was 8.7 per cent compared with 10.7 per cent with a statin alone (relative risk reduction 19 per cent). A similar relative risk reduction in patients with no CHD was not statistically significant. There was no difference in mortality between the groups but EPA did reduce unstable angina and nonfatal coronary events. Department pilots information prescriptions The Department of Health has announced 20 sites to pilot information prescriptions prior to a nationwide roll-out in 2008. The prescriptions will guide people with long-term conditions such as diabetes and cancer to sources of support and information about their condition. The Department hopes the project will increase patients' understanding of their discussions with health professionals, empower them to locate the information they need, and provide long-term support. NPSA guidelines for safer prescribing The National Patient Safety Agency (www.npsa.nhs.uk) has published five guidelines to improve medication safety in the NHS. Targeting ,high-risk issues', the guidance covers anticoagulant prescribing, liquid medicines for oral or enteral administration, injectable medicines, epidural injections and infusions, and paediatric intravenous infusions. The implementation of each guide is supported by additional tools and resources. Better adherence not matched to outcomes A systematic review has found that interventions can increase adherence to prescribed medication but there is no evidence that clinical outcomes also improve (Arch Intern Med 2007;167:540-9). The review of 37 trials identified 20 reporting increased adherence. The most effective interventions were behavioural changes to reduce dose demands and those involving monitoring and feedback. Improvements in clinical outcomes were variable and did not correspond to changes in adherence. Antidepressant plus mood stabiliser no better US investigators have found that combining a mood stabiliser with an antidepressant is no more effective than a mood stabiliser alone in preventing mood changes (N Engl J Med 2007; published online 28 March, doi.10.1056/NEJMoa064135). The study found durable recovery occurred in 23.5 per cent of patients treated with a mood stabiliser and adjunctive antidepressant therapy for six months compared with 27.3 per cent of those taking a mood stabiliser plus placebo. [source] De novo expression of Kv6.3 contributes to changes in vascular smooth muscle cell excitability in a hypertensive mice strainTHE JOURNAL OF PHYSIOLOGY, Issue 3 2009Alejandro Moreno-Domínguez Essential hypertension involves a gradual and sustained increase in total peripheral resistance, reflecting an increased vascular tone. This change associates with a depolarization of vascular myocytes, and relies on a change in the expression profile of voltage-dependent ion channels (mainly Ca2+ and K+ channels) that promotes arterial contraction. However, changes in expression and/or modulation of voltage-dependent K+ channels (Kv channels) are poorly defined, due to their large molecular diversity and their vascular bed-specific expression. Here we endeavor to characterize the molecular and functional expression of Kv channels in vascular smooth muscle cells (VSMCs) and their regulation in essential hypertension, by using VSMCs from resistance (mesenteric) or conduit (aortic) arteries obtained from a hypertensive inbred mice strain, BPH, and the corresponding normotensive strain, BPN. Real-time PCR reveals a differential distribution of Kv channel subunits in the different vascular beds as well as arterial bed-specific changes under hypertension. In mesenteric arteries, the most conspicuous change was the de novo expression of Kv6.3 (Kcng3) mRNA in hypertensive animals. The functional relevance of this change was studied by using patch-clamp techniques. VSMCs from BPH arteries were more depolarized than BPN ones, and showed significantly larger capacitance values. Moreover, Kv current density in BPH VSMCs is decreased mainly due to the diminished contribution of the Kv2 component. The kinetic and pharmacological profile of Kv2 currents suggests that the expression of Kv6.3 could contribute to the natural development of hypertension. [source] Prostanoid release and constrictor responses to noradrenaline in the rat mesenteric vascular bed in non-insulin-dependent diabetes mellitusAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2001H. A. Peredo 1,The administration of streptozotocin (STZ) to 2-day old rats induced a non-insulin-dependent diabetes mellitus (NIDDM)-like state, with mild hyperglycaemia and no alterations in body weight at the adult age. 2,In the isolated and perfused mesenteric vascular bed of NIDDM animals, the constrictor responses to either noradrenaline (NA) or potassium chloride (KCl) were not modified as compared with age-matched non-diabetic controls. 3,The reduction in NA contractions induced by the cyclooxygenase inhibitor, 10 ,M indomethacin in the control group was absent in the NIDDM rats. 4,The increase in the NA-induced contractions caused by endothelium removal was suppressed by indomethacin in the controls but not in the NIDDM group. 5,The prostanoid release from the mesenteric vascular beds of NIDDM rats was markedly reduced as compared with non-diabetic controls. Noradrenaline increased production of the constrictor prostaglandin (PG) F2, in control but not in NIDDM rats. 6,In summary, these results show that in STZ-induced NIDDM rats, there is an impairment of the prostanoid production, as well as a suppression of the role of prostanoids in the contractile effects of NA in the mesenteric vascular bed. These alterations are more severe than those previously observed in a model of insulin-dependent diabetes mellitus (IDDM), in which hyperglycaemia and reduction of body weight were more marked. The conclusion is that, in these models of diabetes and in the preparation studied, vascular alterations and modifications of glycaemia and body weight are not closely related. [source] Acute hypertension reveals depressor and vasodilator effects of cannabinoids in conscious ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009W-S Vanessa Ho Background and purpose:, The cardiovascular effects of cannabinoids can be influenced by anaesthesia and can differ in chronic hypertension, but the extent to which they are influenced by acute hypertension in conscious animals has not been determined. Experimental approach:, We examined cardiovascular responses to intravenous administration of anandamide and the synthetic cannabinoid, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55212-2), in conscious male Wistar rats made acutely hypertensive by infusion of angiotensin II (AII) and arginine vasopressin (AVP). Rats were chronically instrumented for measurement of arterial blood pressure and vascular conductances in the renal, mesenteric and hindquarters beds. Key results:, Anandamide dose-dependently decreased the mean arterial blood pressure of rats made hypertensive by AII-AVP infusion, but not normotensive rats. Interestingly, acute hypertension also revealed a hypotensive response to WIN55212-2, which caused hypertension in normotensive animals. The enhanced depressor effects of the cannabinoids in acute hypertension were associated with increased vasodilatation in hindquarters, renal and mesenteric vascular beds. Treatment with URB597, which inhibits anandamide degradation by fatty acid amide hydrolase, potentiated the depressor and mesenteric vasodilator responses to anandamide. Furthermore, haemodynamic responses to WIN55212-2, but not to anandamide, were attenuated by the CB1 receptor antagonist, AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide]. Conclusions and implications:, These results broadly support the literature showing that the cardiovascular effects of cannabinoids can be exaggerated in hypertension, but highlight the involvement of non-CB1 receptor-mediated mechanisms in the actions of anandamide. [source] In vitro and in vivo pharmacological characterization of the novel UT receptor ligand [Pen5,DTrp7,Dab8]urotensin II(4,11) (UFP-803)BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2006Valeria Camarda The novel urotensin-II (U-II) receptor (UT) ligand, [Pen5,DTrp7,Dab8]U-II(4,11) (UFP-803), was pharmacologically evaluated and compared with urantide in in vitro and in vivo assays. In the rat isolated aorta, UFP-803 was inactive alone but, concentration dependently, displaced the contractile response to U-II to the right, revealing a competitive type of antagonism and a pA2 value of 7.46. In the FLIPR [Ca2+]i assay, performed at room temperature in HEK293hUT and HEK293rUT cells, U-II increased [Ca2+]i with pEC50 values of 8.11 and 8.48. Urantide and UFP-803 were inactive as agonists, but antagonized the actions of U-II by reducing, in a concentration-dependent manner, the agonist maximal effects with apparent pKB values in the range of 8.45,9.05. In a separate series of experiments performed at 37°C using a cuvette-based [Ca2+]i assay and CHOhUT cells, urantide mimicked the [Ca2+]i stimulatory effect of U-II with an intrinsic activity (,) of 0.80, while UFP-803 displayed a small (,=0.21) but consistent residual agonist activity. When the same experiments were repeated at 22°C (a temperature similar to that in FLIPR experiments), urantide displayed a very small intrinsic activity (,=0.11) and UFP-803 was completely inactive as an agonist. In vivo in mice, UFP-803 (10 nmol kg,1) antagonized U-II (1 nmol kg,1)-induced increase in plasma extravasation in various vascular beds, while being inactive alone. In conclusion, UFP-803 is a potent UT receptor ligand which displays competitive/noncompetitive antagonist behavior depending on the assay. While UFP-803 is less potent than urantide, it displayed reduced residual agonist activity and as such may be a useful pharmacological tool. British Journal of Pharmacology (2006) 147, 92,100. doi:10.1038/sj.bjp.0706438 [source] Review Article: Ocular blood flow assessment using continuous laser Doppler flowmetryACTA OPHTHALMOLOGICA, Issue 6 2010Charles E. Riva Acta Ophthalmol. 2010: 88: 622,629 Abstract. This article describes the technique of continuous laser Doppler flowmetry (LDF) as applied to the measurement of the flux of red blood cells in the optic nerve head, iris and subfoveal choroid. Starting with the exposition of the physical principles underlying LDF, we first describe the various devices developed to perform LDF in these vascular beds. We then discuss the clinical protocols, blood flow parameters, calibration procedures, reproducibility and limitations of the LDF technique. Various problems still need to be solved in order to bring to light the full potential of LDF in the assessment of microcirculatory haemodynamics. [source] Role of NO in retinal vascular diseaseACTA OPHTHALMOLOGICA, Issue 2009L SCHMETTERER Purpose Nitric oxide (NO) is a key regulator of vascular tone in all vascular beds including the eye. Hence, inhibition of NO synthase with L-arginine analogues leads to a reduction of blood flow to all ocular tissues. This enables the investigation of the role of NO in the physiology of blood flow regulation, but also abnormalities of the vascular L-arginine/NO system in ocular vascular disease. Methods A variety of studies investigating the role of NO in healthy humans but also in patients with vascular disease is summarized. Results Inhibition of NO synthase reduces retinal, choroidal and optic nerve head blood. A variety of studies also indicate that NO plays a role in the ocular vasodilator effects of numerous agonists including acetylcholine, bradykinin, carbon dioxide, histamine and insulin. In addition, NO appears to modulate the autoregulatory behavior of ocular vascular beds and is involved in retinal neurovascular coupling. In several ocular diseases such as diabetic retinopathy or open angle glaucoma abnormalities in the NO system can be observed. Conclusion NO is a major regulator of ocular blood flow in humans. The existence of different NO synthase isoforms makes it, however, difficult to therapeutically intervent via the L-arginine/NO pathway. Further studies are required to characterize the role of the NO synthase isoforms in the control of ocular blood flow in more detail and to allow for therapeutic interventions in ischemic ocular eye disease via this attractive pathway. [source] Ocular blood flow autoregulation and the clinical implications of its alterationACTA OPHTHALMOLOGICA, Issue 2009G GARHOFER Autoregulation is commonly defined as the ability of a vascular bed to adapt blood flow to changes in ocular perfusion pressure (pressure autoregulation) or to adapt to changes in metabolic need (metabolic autoregulation). Considering the high metabolic turnover of the eye, its intact function is strongly dependent on a stable blood supply, assured by an intact vascular autoregulation. However, it has been shown that in the recent years that several ocular diseases such as glaucoma, diabetic retinopathy or age related macula degeneration are associated with an impaired autoregulation. This vascular dysregulation may lead to an under- or overperfusion of the tissue and in turn to ischemia and/or oxidative stress. This talk seeks to summarize our current knowledge of autoregulation in the ocular vascular beds. Furthermore, the possible reasons of impaired autoregulation and how this may relate to ocular pathologies will be discussed. [source] Most readily usable methods to measure ocular blood flowACTA OPHTHALMOLOGICA, Issue 2009K GUGLETA Purpose SIS Lecture. Methods Literature search. Results Ocular Blood Flow Research Association (OBFRA, recently merged with another organization - ISOCO, into one single Association for Ocular CDirculation - AOC) made a significant contribution to standardization of the blood flow measuring techniques in the field of ophthalmology. A consens was reached on the number of OBF measurements techniques that occured in the past decades. Particular emphasis was placed on the basic technology, specific parameters and interpretation, accuracy and reproducibility, field of clinical applications. Open questions were extensively discussed, limits of each technique clearly postulated. and a consensus statement put together for each of the technique involved. It encompassed techniques like color Doppler imaging, laser Doppler flowmetry (continuous as well as scanning LDF), laser Doppler velocimetry, Retinal Vessel Analyzer, combination of the vessel diameter measurement and the LDV, laser interferometry of the fundus pulsations amplitude, retinal oxymetry, measurements of the pulsatile component of the blood flow, blue field entoptic method and the newest - Doppler OCT. Conclusion There is no overwhelming measuring technique able to cover all the aspects of the research and the daily clinical routine. Various parameters and various vascular beds are involved, which makes the interpretation of the obtained results strenuous. Of particular importance is the capability of OBF measuring techniques to capture one dynamic feature of ocular circulation - its ability to regulate and to response to various challenges. It is widely believed that not the constantly reduced blood flow, but rather the lack of regulation thereof, leads to prevalent ocular diseases. [source] PHYSIOLOGICAL SLEEP-DEPENDENT CHANGES IN ARTERIAL BLOOD PRESSURE: CENTRAL AUTONOMIC COMMANDS AND BAROREFLEX CONTROLCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2008Alessandro Silvani SUMMARY 1Sleep is a heterogeneous behaviour. As a first approximation, it is subdivided objectively into two states: non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS). 2The mean value and variability of arterial blood pressure (ABP) decrease physiologically from wakefulness to NREMS. In REMS, there may be a further decrease or increase in mean ABP as well as phasic hypertensive events, which enhance the variability of ABP. 3The reduced mean ABP during NREMS results from a decrease in either heart rate or sympathetic vasoconstrictor tone. During REMS, sympathetic activity to the different cardiovascular effectors undergoes a substantial repatterning. Thus, the mean ABP in REMS reflects a balance between changes in cardiac output and constriction or dilatation of different vascular beds. 4In both sleep states, the phasic changes in ABP are driven by bursts of vasoconstriction, which may be accompanied by surges of heart rate. 5The available evidence supports the hypothesis that the sleep-dependent changes in ABP, either tonic or phasic, result from the integration between cardiovascular reflexes and central autonomic commands that are specific to each sleep state. [source] Functional Roles Of KATP Channels In Vascular Smooth MuscleCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2002Joseph E Brayden SUMMARY 1. ATP-sensitive potassium channels (KATP) are present in vascular smooth muscle cells and play important roles in the vascular responses to a variety of pharmacological and endogenous vasodilators. 2. The KATP channels are composed of four inwardly rectifying K+ channel subunits and four regulatory sulphonylurea receptors. The KATP channels are inhibited by intracellular ATP and by sulphonylurea agents. 3. Pharmacological vasodilators such as cromakalim, pinacidil and diazoxide directly activate KATP channels. The associated membrane hyperpolarization closes voltage-dependent Ca2+ channels, which leads to a reduction in intracellular Ca2+ and vasodilation. 4. Endogenous vasodilators such as calcitonin gene-related peptide, vasoactive intestinal polypeptide, prostacylin and adenosine activate KATP by stimulating the formation of cAMP and increasing the activity of protein kinase A. Part of the mechanism of contraction of endogenous vasoconstrictors is due to inhibition of KATP channels. 5. The KATP channels appear to be tonically active in some vascular beds and contribute to the physiological regulation of vascular tone and blood flow. These channels also are activated under pathophysiological conditions, such as hypoxia, ischaemia, acidosis and septic shock, and, in these disease states, may play an important role in the regulation of tissue perfusion. [source] | |||||||||||||||||||||||||