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Pressure Regulation (pressure + regulation)
Kinds of Pressure Regulation Selected AbstractsBlood Pressure Regulation and Vegetarian DietsNUTRITION REVIEWS, Issue 1 2005Susan E. Berkow PhD Hypertension affects approximately 50 million individuals in the United States and approximately 1 billion worldwide. Although heredity plays a role in blood pressure variability, diet and lifestyle exert considerable influence in blood pressure regulation. This report reviews the evidence of the relationship between a vegetarian diet and blood pressure regulation and presents data as to the putative mechanisms of action. [source] Optimal Pressure Regulation of the Pneumatic Ventricular Assist Device With Bellows-Type DriverARTIFICIAL ORGANS, Issue 8 2009Jung Joo Lee Abstract The bellows-type pneumatic ventricular assist device (VAD) generates pneumatic pressure with compression of bellows instead of using an air compressor. This VAD driver has a small volume that is suitable for portable devices. However, improper pneumatic pressure setup can not only cause a lack of adequate flow generation, but also cause durability problems. In this study, a pneumatic pressure regulation system for optimal operation of the bellows-type VAD has been developed. The optimal pneumatic pressure conditions according to various afterload conditions aiming for optimal flow rates were investigated, and an afterload estimation algorithm was developed. The developed regulation system, which consists of a pressure sensor and a two-way solenoid valve, estimates the current afterload and regulates the pneumatic pressure to the optimal point for the current afterload condition. Experiments were performed in a mock circulation system. The afterload estimation algorithm showed sufficient performance with the standard deviation of error, 8.8 mm Hg. The flow rate could be stably regulated with a developed system under various afterload conditions. The shortcoming of a bellows-type VAD could be handled with this simple pressure regulation system. [source] Relationship between breathing and cardiovascular function at rest: sex-related differencesACTA PHYSIOLOGICA, Issue 2 2010B. G. Wallin Abstract Aim:, To compare relationships at rest between breathing rate, levels of muscle sympathetic nerve activity, total peripheral resistance and cardiac output among young men and women. Methods:, Recordings were made of respiratory movements, sympathetic nerve activity (peroneal microneurography), intra-arterial blood pressure, electrocardiogram, cardiac output (open-circuit acetylene uptake technique) in 19 healthy men (age 27 ± 2 years, mean ± SEM) and 17 healthy women (age 25 ± 1 years). Total peripheral resistance and stroke volume were calculated. Four minutes epochs of data were analysed. Results:, Breathing rates and sympathetic activity were similar in men and women but compared to men, women had significantly lower blood pressures, cardiac output and stroke volume. In men breathing rate correlated positively with sympathetic activity (r = 0.58, P < 0.05) but not in women (r = 0.12, P > 0.05). Furthermore, in men, respiratory rate correlated positively with total peripheral resistance (r = 0.65, P < 0.05) and inversely with cardiac output (r = ,0.84, P < 0.05) and heart rate (r = ,0.60, P < 0.05) but there were no such relationships in women (P > 0.05 for all). Conclusions:, The positive relationship between breathing and sympathetic activity in men, and the inverse coupling of breathing to cardiac output and heart rate suggest that influences of respiration may be important not only for dynamic but also for ,tonic' cardiovascular function. The lack of relationships among these variables in women shows that there are fundamental differences in basic blood pressure regulation between the sexes. [source] Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidantsACTA PHYSIOLOGICA, Issue 4 2007M. P. Koeners Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 ± 4 vs. 33 ± 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 ± 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source] Association analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart StudyDIABETIC MEDICINE, Issue 3 2006K. P. Burdon Abstract Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin-angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima-media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population. [source] A sympathetic view of the sympathetic nervous system and human blood pressure regulationEXPERIMENTAL PHYSIOLOGY, Issue 6 2008Michael J. Joyner New ideas about the relative importance of the autonomic nervous system (and especially its sympathetic arm) in long-term blood pressure regulation are emerging. It is well known that mean arterial blood pressure is normally regulated in a fairly narrow range at rest and that blood pressure is also able to rise and fall ,appropriately' to meet the demands of various forms of mental, emotional and physical stress. By contrast, blood pressure varies widely when the autonomic nervous system is absent or when key mechanisms that govern it are destroyed. However, 24 h mean arterial pressure is still surprisingly normal under these conditions. Thus, the dominant idea has been that the kidney is the main long-term regulator of blood pressure and the autonomic nervous system is important in short-term regulation. However, this ,renocentric' scheme can be challenged by observations in humans showing that there is a high degree of individual variability in elements of the autonomic nervous system. Along these lines, the level of sympathetic outflow, the adrenergic responsiveness of blood vessels and individual haemodynamic patterns appear to exist in a complex, but appropriate, balance in normotension. Furthermore, evidence from animals and humans has now clearly shown that the sympathetic nervous system can play an important role in longer term blood pressure regulation in both normotension and hypertension. Finally, humans with high baseline sympathetic traffic might be at increased risk for hypertension if the ,balance' among factors deteriorates or is lost. In this context, the goal of this review is to encourage a comprehensive rethinking of the complexities related to long-term blood pressure regulation in humans and promote finer appreciation of physiological relationships among the autonomic nervous system, vascular function, ageing, metabolism and blood pressure. [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] Melatonin: therapeutic and clinical utilizationINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2007A. Altun Summary Melatonin, acting through melatonin receptors, is involved in numerous physiological processes including circadian entrainment, blood pressure regulation, oncogenesis, retinal physiology, seasonal reproduction, ovarian physiology, immune function and most recently in inducing osteoblast differentiation. Moreover, melatonin was proved to be a potent-free radical scavenger and a broad-spectrum antioxidant. More research is required into the effects of therapeutically modulating the melatoninergic system on circadian haemodynamics and rhythm under varying physiopathological conditions and the possible impact on morbidity and mortality in humans. [source] Renal cortex remodeling in nitric oxide deficient rats treated with enalaprilJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2004Noemi Barbuto Abstract The kidney NO synthase is one of the most important renal controlling systems. This paper aims the quantification of renal cortical components involved in blood pressure regulation under NOs blockade. Spontaneous hypertensive rats (SHRs) are submitted to chronic blockade of NOs by L-nitro-arginine-methyl-ester (L-NAME) and an ACE inhibitor (enalapril) in comparison with the normotensive Wistar rats. Twenty SHRs and 5 Wistar rats were divided in 5 groups and observed for 21 days for blood pressure (BP) and serum creatinine: control Wistar (5) (C-W), control SHR (5) (C-SHR), L-SHR (5) - received L-NAME 30 mg/kg/day, L+E-SHR (5) - received L-NAME and Enalapril maleate 15 mg/kg/day, E-SHR (5) - received Enalapril maleate. A quantitative morphometric study (glomerular density, QA[g1], interstitium volume density, Vv[i], tubular surface and length densities, Sv[t] and Lv[t]) were performed at the end. The BP reached 226±15 mmHg in L-SHR group. The BP difference between the L-SHR and the C-SHR groups was significant from the first week while the E-SHR group became significant from the second week. At the end of the experiment the BP of the E-SHR group was similar to the BP in the C-W group. The QA[g1] was similar among C-SHR, L-SHR and L+E-SHR groups and no difference was found between E-SHR and C-W groups. In the L-SHRs serum creatinine was greatly increased, and microscopy showed thickening of arteriolar tunica media with an increase of the wall-to-lumen ratio, perivascular fibrosis, inflammatory infiltrated, tubular atrophy and interstitial fibrosis with focal segmental glomerulosclerosis. The use of enalapril was not completely efficient in reducing BP and morphological injury when the hypertension of SHRs was increased with the NOs blockade suggesting that NO deficiency-induced hypertension is not entirely mediated by the RAAS. [source] Studies on the molecular recognition between bioactive peptides and angiotensin-converting enzymeJOURNAL OF MOLECULAR RECOGNITION, Issue 2 2009A.S. Pina Abstract High blood pressure or hypertension is a condition affecting many individuals and represents a controllable risk factor for cardiovascular diseases such as coronary heart disease and stroke. A non-pharmacological approach to manage these includes the application of food components with antihypertensive activity. Milk protein-derived peptides have been exploited as natural hypotensive agents, namely the peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), already commercialized in functional foods as a potential alternative to synthetic drugs. These bioactive peptides inhibit in vitro and in vivo the Angiotensin I-converting enzyme (ACE), a protein with an important role in blood pressure regulation. In this work, we attempted to elucidate the possible mode of interaction between the peptides and ACE, including mechanisms of binding to the cofactor Zn2+, and further contrast this with the known mode of inhibition exerted by synthetic drugs (Captopril, Enalaprilat and Lisinopril). The bioactive peptide Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR), also known to inhibit the enzyme ACE but with a lower efficiency than VPP and IPP, was utilized in the docking studies for comparison. It was observed that the best docking poses obtained for VPP and IPP were located at the ACE catalytic site with very high resemblance to the drugs mode of interaction, including the coordination with Zn2+. As for ALPMHIR, the best docking poses were located in the narrow ACE channel outside the catalytic site, representing higher affinity energies and fewer resemblances with the interaction established by drugs. Copyright © 2008 John Wiley & Sons, Ltd. [source] Human brain aminopeptidase A: biochemical properties and distribution in brain nucleiJOURNAL OF NEUROCHEMISTRY, Issue 1 2008Nadia De Mota Abstract Aminopeptidase A (APA) generated brain angiotensin III, one of the main effector peptides of the brain renin angiotensin system, exerting a tonic stimulatory effect on the control of blood pressure in hypertensive rats. The distribution of APA in human brain has not been yet studied. We first biochemically characterized human brain APA (apparent molecular mass of 165 and 130 kDa) and we showed that the human enzyme exhibited similar enzymatic characteristics to recombinant mouse APA. Both enzymes had similar sensitivity to Ca2+. Kinetic studies showed that the Km (190 ,mol/L) of the human enzyme for the synthetic substrate- l -glutamyl-,-naphthylamide was close from that of the mouse enzyme (256 ,mol/L). Moreover, various classes of inhibitors including the specific and selective APA inhibitor, (S)-3-amino-4-mercapto-butyl sulfonic acid, had similar inhibitory potencies toward both enzymes. Using (S)-3-amino-4-mercapto-butyl sulfonic acid, we then specifically measured the activity of APA in 40 microdissected areas of the adult human brain. Significant heterogeneity was found in the activity of APA in the various analyzed regions. The highest activity was measured in the choroids plexus and the pineal gland. High activity was also detected in the dorsomedial medulla oblongata, in the septum, the prefrontal cortex, the olfactory bulb, the nucleus accumbens, and the hypothalamus, especially in the paraventricular and supraoptic nuclei. Immunostaining of human brain sections at the level of the medulla oblongata strengthened these data, showing for the first time a high density of immunoreactive neuronal cell bodies and fibers in the motor hypoglossal nucleus, the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, the Roller nucleus, the ambiguus nucleus, the inferior olivary complex, and in the external cuneate nucleus. APA immunoreactivity was also visualized in vessels and capillaries in the dorsal motor nucleus of the vagus and the inferior olivary complex. The presence of APA in several human brain nuclei sensitive to angiotensins and involved in blood pressure regulation suggests that APA in humans is an integral component of the brain renin angiotensin system and strengthens the idea that APA inhibitors could be clinically tested as an additional therapy for the treatment of certain forms of hypertension. [source] Blood Pressure Regulation and Vegetarian DietsNUTRITION REVIEWS, Issue 1 2005Susan E. Berkow PhD Hypertension affects approximately 50 million individuals in the United States and approximately 1 billion worldwide. Although heredity plays a role in blood pressure variability, diet and lifestyle exert considerable influence in blood pressure regulation. This report reviews the evidence of the relationship between a vegetarian diet and blood pressure regulation and presents data as to the putative mechanisms of action. [source] Sodium, blood pressure, and ethnicity: What have we learned?,AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2009Lillian Gleiberman An enormous amount of research has yielded significant knowledge about ethnic differences in sodium homeostasis and blood pressure regulation. Consistent findings such as greater sodium-sensitivity, lower potassium excretion and high higher serum sodium levels in African Americans need further exploration to define more precise physiological mechanisms. The genetic alleles associated with sodium homeostasis in relation to blood pressure have accounted for only a small proportion of the variance in blood pressure. Several allelic variants differ in frequency among ethnic groups and heat-adapted genetic variants have a high prevalence in low latitudes and hot, wet climates which lends support to the "sodium retention" hypothesis. The blood pressure disparities between African Americans and whites may, in part, be due to different allelic frequencies of genes associated with sodium homeostasis. However, with advances in genomics, environmental factors tend to be neglected in research. Better measures of environmental stress have recently been developed by anthropologists and should be included in research designs by investigators in other disciplines. Public health efforts should encourage food producers to reduce sodium content of its products, and physicians should encourage patients to reduce consumption of high sodium packaged and fast foods. Am. J. Hum. Biol., 2009. © 2009 Wiley-Liss, Inc. [source] Blunted effect of the Kv channel inhibitor on pulmonary circulation in Tibetan sheep: A model for studying hypoxia and pulmonary artery pressure regulationRESPIROLOGY, Issue 1 2004Takeshi Ishizaki Objective: The aim of this study was to assess the effect of 4-aminopyridine, a Kv channel inhibitor, on the pulmonary circulation of Tibetan sheep. It has been reported that chronic hypoxia downregulates the 4-aminopyridine (4AP)-sensitive Kv channel (which governs the membrane potential (Em) of pulmonary vascular smooth muscle cells in pulmonary vessels) without a change in 4AP sensitivity. Methodology: Pulmonary haemodynamic indices and blood gas analyses were measured in six young male animals in an altitude chamber that was adjusted to simulated altitudes of 0 m, 2260 m, and 4500 m. Drip infusion of 4AP, 10 mg/h for 3 h, was started and continued during the study. Results: With the increase in altitude mean pulmonary artery pressure increased and mean Pao2 decreased. 4AP had no effect on the levels of mean PPA, mean pulmonary artery wedge pressure, cardiac output, and mean PaO2, mean PaCO2, and mean pH at any altitude but tended to alter heart rate and mean arterial pressure at altitudes of 2260 m and 4500 m. Conclusion: It is concluded that the 4AP-sensitive Kv channel does not play a role in pulmonary vascular tone in high-altitude active Tibetan sheep. Their pulmonary vascular oxygen sensing appears not to involve Kv channels. [source] ORIGINAL ARTICLE: Leptin Gene (TTTC)n Microsatellite Polymorphism as well as Leptin Receptor R223Q and PPAR,2 P12A Substitutions are not Associated with Hypertensive Disorders in PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Annette Wiedemann Citation Wiedemann A, Vocke F, Fitzgerald JS, Markert UR, Jeschke U, Lohse P, Toth B. Leptin gene (TTTC)n microsatellite polymorphism as well as Leptin receptor R223Q and PPAR,2 P12A substitutions are not associated with hypertensive disorders in pregnancy. Am J Reprod Immunol 2010; 63: 310,317 Problem, Pregnancy-induced hypertension (PIH) affects up to 15% of all pregnancies. Disturbed placentation is one factor associated with PIH. Leptin and peroxisome proliferator activator receptors (PPAR) seem to play an important role in placentation, fetal development, and blood pressure regulation. Therefore, we investigated polymorphisms in the genes encoding leptin, the leptin receptor, and PPAR,2 in patients with PIH. Method of study, In this retrospective case,control study, 103 patients with PIH [gestational hypertension (GH) n = 39; preeclampsia n = 27; eclampsia n = 5; HELLP n = 32] and 100 controls were analyzed for the LEP tetranucleotide repeat (TTTC)n and the leptin receptor (LEPR) R223Q and PPAR,2 P12A substitutions. Statistical analysis was performed using the chi-square, Mann,Whitney U -, and Kruskal,Wallis tests (P < 0.05 significant). Results, The frequency of the three possible genotypes did not differ significantly between patients and controls [LEP (TTTC)n: P = 0.43; LEPR R223Q: P = 0.94; PPAR,2 P12A: P = 0.94]. However, postpartal diastolic blood pressure of PIH patients was significantly higher in homozygous carriers of the LEPR Q223-encoding allele as compared with patients carrying the wild-type allele (P < 0.01). Conclusion, Hypertensive disorders in pregnancy were not associated with the LEP, LEPR, and PPAR,2 polymorphisms studied. The role of other variations in the LEP and PPAR genes in the pathophysiology of PIH and in exacerbations are the objective of ongoing research. [source] The obligatory role of the kidney in long-term arterial blood pressure control: extending Guyton's model of the circulationANAESTHESIA, Issue 11 2009K. L. Dorrington Summary We describe a model for the essential role of the kidney in long-term blood pressure regulation. We begin with a simple hydraulic model for the circulation, with a constant circulating volume. We show, with the help of a modification of Guyton's classic diagram, that cardiac output and mean arterial pressure are functions of circulating volume, peripheral resistance, venous and arterial compliances, and the cardiac Starling curve. This approach models only acute changes in a ,closed' circulation , one where there is no intake or excretion of fluid. The model is then adapted to ,open' the circulation, include a role for the kidney, and represent more chronic changes. Arterial pressure is then a sole function of renal behaviour and daily sodium (and liquid) intake, and becomes independent of other cardiovascular variables. As well as generating specific hypotheses for further investigation, these models can be used for the purpose of education in cardiovascular control and the treatment of hypertension. [source] Histological Assessment of Selected Blood Vessels of the Phocid Seals (Northern Elephant and Harbour Seals)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2010H. Smodlaka Summary Phocid seals exhibit vascular adaptations that allow them to undertake prolonged deep dives. These vascular adaptations are either unique to phocids, or are modified vascular equivalents to those present in terrestrial mammals. One such adaptation, the aortic bulb, is a spherical enlargement of the ascending aorta specific to phocid seals. Its histological make-up consists of a reinforced tunica media with circular and longitudinal layers of elastic fibres. This reinforcement enables multi-axial deformation of the aortic bulb, thus complementing its function as a prominent elastic reservoir or ,windkessel'. A second adaptation, the hepatic sinus, is an asymmetrical dilation of the abdominal portion of the caudal vena cava and accompanying hepatic veins. The hepatic sinus is comprised of a relatively thin tunica media, with a scant smooth muscle component. The bulk of the sinus wall is comprised of tunica adventitia. A third vascular adaptation distinctive to the phocids is the pericardial venous plexus, composed of convoluted veins circumnavigating the perimeter of the heart. Microscopically, these veins have a thick tunica media and also contain valves. Smaller arteries, venules and distinct capillary beds are observed interspersed in-between these veins. It can be hypothesized, that in seals, certain vascular embryonic development may be arrested at an earlier embryonic stage, resulting in these unusual vascular formations. These modifications play a vital role in blood pressure regulation and distribution of oxygenated blood during prolonged deep diving. The purpose of this work was to elucidate the histological aspects of these unique vascular modifications and relate them to specific function. [source] Comparative in vitro degradation of the human hemorphin LVV-H7 in mammalian plasma analysed by capillary zone electrophoresis and mass spectrometryBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2007Harald John Abstract The human hemorphin LVV-H7 (L32VVYPWTQRF41) is a hemoglobin-,, -,, -, or -, chain derived cationic decapeptide of the µ-opioid receptor binding family. It exhibits potential pharmacological value relevant, for example, for blood pressure regulation, learning performance and Alzheimer's disease. The regulatory potency is strictly dependent on the length of the amino acid sequence which is sensitive towards proteinases from tissues and plasma. To analyse LVV-H7 in vitro degradation in mammalian plasma, a novel multi-component quantitative capillary zone electrophoretic (CZE) procedure was applied, combined with qualitative metabolite profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In all types of plasma, LVV-H7 was N -terminally truncated generating four metabolites (M1,M4) with an intact C -terminus: M1 (V33VYPWTQRF41), M2 (V34YPWTQRF41), M3 (Y35PWTQRF41) and M4 (W37TQRF41). In EDTA plasma these degradation products were detected exclusively, whereas in citrate and heparin plasma four further metabolites appeared resulting from additional C -terminal cleavage of the dipeptide R40F41: M5 (L32VVYPWTQ39), M6 (V33VYPWTQ39), M7 (V34YPWTQ39) and M8 (Y35PWTQ39). In the presence of selective proteinase inhibitors aminopeptidase M and angiotensin-converting enzyme (for N - and C -terminal truncation, respectively) were identified as plasma enzymes responsible for hemorphin degradation. Furthermore, striking inter-mammalian species distinctions were detected revealing strongly differing degradation velocities but similar metabolite patterns. Copyright © 2007 John Wiley & Sons, Ltd. [source] Possible involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressor responses to platelet activating factor (PAF) in ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2000Yoshio Tanaka In anaesthetized rats, platelet activating factor (PAF; 1 ,g kg,1) decreased mean arterial blood pressure by around 60 mmHg (n=18). This depressor response was completely blocked by the PAF antagonist, CV-6209 (1 mg kg,1), indicating the role of PAF-specific receptor in the response. NG -nitro- L -arginine methyl ester (L -NAME; 50 mg kg,1), an NO synthase inhibitor, profoundly elevated systemic blood pressure (n=19), indicating an important role of NO in the basal blood pressure regulation. The depressor response to PAF (1 ,g kg,1) normalized against that to sodium nitroprusside (SNP) (10 ,g kg,1) was not substantially different between rats treated without and with L -NAME (n=4). In contrast, the depressor effect of acetylcholine (0.03,1.0 ,g kg,1) normalized against that of SNP (10 ,g kg,1) was significantly attenuated by L -NAME (n=5). Charybdotoxin (0.4 mg kg,1) plus apamin (0.2 mg kg,1) significantly attenuated the depressor response to PAF (1 ,g kg,1) (n=5) without affecting the blood pressure change due to SNP (1 mg kg,1) (n=3). Charybdotoxin (0.4 mg kg,1) (n=4) or apamin (0.2 mg kg,1) (n=4) alone did not affect the PAF-induced depressor response. These findings suggest that EDHF may make a significant contribution to the depressor response to PAF in rats. Although NO plays the determinant role in the basal blood pressure regulation, its contribution to PAF-produced depressor response seems to be less as compared with that to the depressor response to acetylcholine. British Journal of Pharmacology (2000) 131, 1113,1120; doi:10.1038/sj.bjp.0703681 [source] ROLE OF HYPOTHALAMIC ,2 -ADRENOCEPTOR ACTIVITY IN FRUCTOSE-INDUCED HYPERTENSIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2006Marcos A Mayer SUMMARY 1The aim of the present study was to investigate the effects of the ,2 -adrenoceptor antagonist yohimbine on blood pressure and heart rate (HR) regulation, as well as on adrenergic and serotoninergic neurotransmission, in fructose hypertensive (F) rats. 2The anterior hypothalamic area of control (C) and F rats was perfused with Ringer's solution containing 10 and 100 µg/mL yohimbine through a microdialysis concentric probe. The effects of yohimbine on mean arterial pressure (MAP) and HR, as well as on hypothalamic dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) levels, were measured according to perfusion time. 3Although intrahypothalamic perfusion of yohimbine increased blood pressure in C rats (,MAP 9 ± 1 and 11 ± 2 mmHg for 10 and 100 µg/mL yohimbine, respectively; P < 0.05 vs Ringer's perfusion), the ,-adrenoceptor antagonist did not modify MAP in F. Intrahypothalamic yohimbine had no effect on HR at either concentration tested. Intrahypothalamic perfusion of 10 and 100 µg/mL yohimbine increased DOPAC levels in C rats (135 ± 6 and 130 ± 5% of basal levels, respectively; both n = 6; P < 0.05 vs Ringer's perfusion), but not in F animals (115 ± 6 and 102 ± 6% of basal levels, respectively; both n = 6). In both C and F rats, yohimbine administration induced an increase in 5-HIAA dialysate levels. 4The results of the present study support the notion that ,2 -adrenoceptor tone of the anterior hypothalamus of normotensive rats, which contributes to normal blood pressure regulation, is not involved in the control of HR in either normotensive C or hypertensive F rats. The absence of changes in MAP after yohimbine perfusion in F rats suggests that the ,2 -adrenoceptor tone could be decreased in this group of rats and that this may be responsible for the maintenance of hypertension in this model. Intrahypothalamic perfusion of yohimbine increased DOPAC in the dialysate only in C rats, suggesting changes in presynaptic ,2 -adrenoceptor activity in fructose-overloaded rats. Conversely, increased 5-HIAA levels did not differ between C and F groups. [source] MECHANISMS MEDIATING PRESSURE NATRIURESIS: WHAT WE KNOW and WHAT WE NEED TO FIND OUTCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2005Roger G Evans SUMMARY 1.,It is well established that pressure natriuresis plays a key role in long-term blood pressure regulation, but our understanding of the mechanisms underlying this process is incomplete. 2.,Pressure natriuresis is chiefly mediated by inhibition of tubular sodium reabsorption, because both total renal blood flow and glomerular filtration rate are efficiently autoregulated. Inhibition of active sodium transport within both the proximal and distal tubules likely makes a contribution. Increased renal interstitial hydrostatic pressure (RIHP) likely inhibits sodium reabsorption by altering passive diffusion through paracellular pathways in ,leaky' tubular elements. 3.,Nitric oxide and products of cytochrome P450-dependent arachidonic acid metabolism are key signalling mechanisms in pressure natriuresis, although their precise roles remain to be determined. 4.,The key unresolved question is, how is increased renal artery pressure ,sensed' by the kidney? One proposal rests on the notion that blood flow in the renal medulla is poorly autoregulated, so that increased renal artery pressure leads to increased renal medullary blood flow (MBF), which, in turn, leads to increased RIHP. An alternative proposal is that the process of autoregulation of renal blood flow leads to increased shear stress in the preglomerular vasculature and, so, release of nitric oxide and perhaps products of cytochrome P450-dependent arachidonic acid metabolism, which, in turn, drive the cascade of events that inhibit sodium reabsorption. 5.,Central to the arguments underlying these opposing hypotheses is the extent to which MBF is autoregulated. This remains highly controversial, largely because of the limitations of presently available methods for measurement of MBF. [source] Angiotensin I-Converting Enzyme And Metabolism Of The Haematological Peptide N -Acetyl-Seryl-Aspartyl-Lysyl-ProlineCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2001Michel Azizi SUMMARY 1. Angiotensin I-converting enzyme (ACE) has two homologous active N- and C-terminal domains and displays activity towards a broad range of substrates. The tetrapeptide N -acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) has been shown to be hydrolysed in vitro by ACE and to be a preferential substrate for its N-terminal active site. This peptide reversibly prevents the recruitment of pluripotent haematopoietic stem cells and normal early progenitors into the S-phase. 2. Angiotensin I-converting enzyme inhibitors, given as a single dose to normal subjects or during long-term treatment in hypertensive patients, result in plasma AcSDKP levels five- to six-fold higher and urine concentrations 40-fold higher than those of control subjects and/or patients. Thus, AcSDKP is a natural peptide hydrolysed by the N-terminal domain of ACE in vivo. In addition, ACE may be implicated in the process of haematopoietic stem cell regulation by permanently degrading this natural circulating inhibitor of cell entry into the S-phase. 3. Besides hydrolysis by ACE, the second very effective mechanism by which AcSDKP is cleared from plasma is glomerular filtration. Because of its high sensitivity and specificity, the measurement of AcSDKP in plasma and urine provides a valuable tool in screening specific inhibitors of the N-terminal domain of ACE and in monitoring ACE inhibition during chronic treatment. 4. The long-term consequences of AcSDKP accumulation are not known. During chronic ACE inhibition in rats, AcSDKP levels slightly increase in organs with high ACE content (kidneys, lungs). To significantly increase its concentration in target haematopoietic organs (the extracellular fraction of bone marrow), AcSDKP has to be infused on top of a captopril-based treatment. 5. A selective inhibitor of the N-domain of ACE in vitro and in vivo has been identified recently. The phosphinic peptide RXP 407 does not interfere with blood pressure regulation, but does increase, dose dependently, plasma concentrations of AcSDKP in mice, in contrast with lisinopril, which affects the metabolism of both AcSDKP and angiotensin I. N-Terminal-selective ACE inhibitors may be used to selectively control AcSDKP metabolism in target haematopoietic organs. This new therapeutic strategy may be of value for protecting haematopoietic cells from the toxicity of cancer chemotherapy. [source] | |||||||||||||