摘要:

During the past decade the simple molecule nitric oxide (NO) has emerged as an important inter- and intracellular messenger regulating many biological functions such as vascular tone, platelet activation and neurotransmission. NO is also an important immunoregulatory molecule with cytostatic and cytotoxic properties [1,2]. The unravelling of the pathways and the role of NO in different cell systems has led to radical changes in the understanding of a wide variety of biological processes. Nowhere has this change been more apparent than in mammalian vascular biology. The present review focuses on NO and the vascular system, and discusses the pathophysiological implications of NO for human vascular disease states.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo determine whether the endothelin-1 or endothelin-3 genes are genetically linked with blood pressure and relative heart weight in segregating rat populations, in the context of an elevated dietary sodium chloride intake.MethodsEndothelin-1 and endothelin-3 genotypes of rats in segregating populations, derived from crosses of Dahl salt-sensitive (SS/Jr) rats with contrasting inbred strains, including Lewis rats, spontaneously hypertensive rats and Dahl salt-resistant (SR/Jr) rats, were determined using restriction fragment length polymorphisms. Segregating populations were fed a high (8%)-sodium chloride diet. Linkage of genotype with blood pressure or relative heart weight was determined by analysis of variance. Chromosomal location of the rat endothelin-3 gene was determined by genotyping a panel of recombinant inbred strains.ResultsTwo alleles for the endothelin-1 gene and three alleles for the endothelin-3 gene were identified. The endothelin-1 locus did not cosegregate with blood pressure or relative heart weight. The endothelin-3 locus cosegregated with blood pressure and relative heart weight in an SS/Jr F1(SS/Jr SR/Jr) population, but not in populations containing a higher percentage of genes from the SR/Jr strain. The endothelin-3 and seminal vesicle protein-1 loci were linked and located on rat chromosome 3.ConclusionThe endothelin-3 gene is, or is linked to, a locus on chromosome 3 that regulates blood pressure and relative heart weight in inbred Dahl rats, and these effects were strongly dependent on the genetic background.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo determine whether taurine reduces blood pressure by stimulating the renal kallikrein—kinin system.MethodsThe effects of taurine on blood pressure, urinary kallikrein activity and renal kallikrein gene expression were investigated in Dahl salt-sensitive (Dahl-S) rats. The specificity of the action of taurine was verified by comparison with the action of β-alanine, a carboxylic analogue of taurine. The effect of co-administration of the specific bradykinin B2 receptor antagonist Hoe 140 was also examined.ResultsAdministration of taurine (3% in drinking water) for 4 weeks retarded the development of salt (4% sodium chloride diet)-induced hypertension. Systolic blood pressure at the end of the experiment was significantly higher in control rats than in taurine-treated rats. Urinary sodium excretion was not decreased by the reduction in blood pressure. The heart weight: body weight ratio was significantly lower, and urinary volume and kallikrein excretion were significantly higher, in taurine-treated rats. Renal kallikrein gene expression at weeks 1 and 4 was higher in taurine-treated rats. Systolic blood pressure 3 and 4 weeks after the administration of β-alanine was slightly, but not significantly, lower than that of untreated rats on a high-salt diet, and was accompanied by a significantly lower body weight. Urinary kallikrein excretion decreased with a high-salt diet regardless of β-alanine administration. Continuous systemic administration of Hoe 140 did not cause any significant alteration in blood pressure in Dahl-S rats that received taurine with a high-salt diet. Taurine also showed a renoprotective effect, as judged by a reduction in proteinuria.ConclusionThese results suggest that taurine is an effective antihypertensive agent for salt-induced hypertension. Although taurine activated renal kallikrein, further studies are required to confirm the participation of activated kallikrein in the antihypertensive, cardioprotective and renoprotective effects of taurine.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo determine the differential calcium responses to two vasoconstrictor peptides, angiotensin II (Ang II) and endothelin-1, in vascular smooth muscle cells derived from mesenteric arteries from young and adult normotensive and hypertensive rats.MethodsEffects of Ang II and endothelin-1 on cytosolic free calcium concentration in primary cultured unpassaged single vascular smooth muscle cells from mesenteric arteries of Wistar-Kyoto (WKY), Wistar and spontaneously hypertensive rats (SHR) aged 3, 9 and 17 weeks were examined microphotometrically using fura-2 methodology.ResultsBasal cytosolic free calcium concentration was significantly increased in cells from SHR aged 9 and 17 weeks compared with cells from age-matched WKY and Wistar rats. Ang II and endothelin-1 significantly increased cell cytosolic free calcium in all rat groups at all ages. Responses to low concentrations of Ang II (1 nmol/l) were significantly higher in cells from SHR aged 9 and 17 weeks than in age-matched controls. This was confirmed in cells from rats aged 17 weeks with full concentration-response curves, which also showed that the pD2for Ang II for WKY rats was significantly different from that of SHR. In cells from SHR at all ages Ang II-stimulated cytosolic free calcium remained persistently high, whereas in cells from WKY and Wistar rats basal levels were reached within 100s after the maximal response. Low concentrations of endothelin-1 elicited significantly lower cytosolic free calcium responses in cells from SHR aged 17 weeks compared with age-matched controls. The time course of cytosolic free calcium responses to endothelin-1 were similar in the groups.ConclusionsIn primary cultured unpassaged mesenteric vascular smooth muscle cells from adult SHR, cytosolic free calcium concentration responses to Angll are enhanced, whereas responses to low concentrations of endothelin-1 are slightly reduced. The differential effects of these two vasoconstrictor peptides may contribute to their relative roles in modulating vascular smooth muscle cell cytosolic free calcium in SHR.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo assess the pharmacological profile of a novel non-peptide endothelin antagonist (50–235) at endothelin receptors in human vascular smooth muscle preparations using radiolabelled binding techniques andin vitropharmacological assays.MethodsThe antagonist was investigated for its ability to inhibit specific [125l]-endothelin-1 binding to ETAand ETBreceptors using cryostat sections of media of human coronary artery. Antagonism by 50–235 (1–30 μmol/l) of endothelin-1-induced vasoconstriction in isolated preparations of human coronary artery, saphenous vein and left internal mammary artery was also determined.ResultsIn coronary artery 50–235 (10-11to 10-4mol/l) inhibited specifically bound [125l]-endothelin-1 (0.1 nmol/l) in a biphasic manner. The ratio of ETA: ETBreceptor was 79:21. Increasing concentrations of 50–235 produced progressive rightwards displacements of the endothelin-1 dose-response curve in each of the three types of blood vessel. The dose-response curves were parallel and no attenuation of the maximum endothelin-1 response was observed suggesting that 50–235 was antagonizing endothelin-1 vasoconstriction in a competitive manner. The pA2values determined by analysis of the Schild regression lines were 6.05 in coronary artery, 6.12 in saphenous vein and 6.18 in left internal mammary artery, and the slopes were not significantly different from unity.ConclusionsThe antagonist 50–235 exhibits nanomolar affinity for human ETAreceptors and 500-fold selectivity for ETAcompared with ETBreceptors. Its novel non-peptide structure demonstrates that the carbon-nitrogen bond is not crucial for endothelin antagonist activity, and might provide important information for the development of therapeutic agents for conditions in which endothelins may be pathophysiologically relevant.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo examine the existence of presynaptic β-adrenoceptors modulating forearm norepinephrine release in 31 healthy volunteers.MethodsThe spillover rate of norepinephrine in forearm venous plasma and the total plasma appearance rate of norepinephrine in the forearm were estimated using intra-arterial infusion of [3H]-norepinephrine. Isoprenaline was infused intra-arterially to stimulate β-adrenoceptors, terbutaline to stimulate β2-adrenoceptors, propranolol to block β-adrenoceptors, metoprolol to block β1-adrenoceptors, isoprenaline combined with metoprolol to stimulate β2-adrenoceptors, epinephrine to stimulate α- and β-adrenoceptors, yohimbine to block α2-adrenoceptors and sodium nitroprusside to increase forearm blood flow directly.ResultsNo systemic hemodynamic effects or changes in arterial plasma norepinephrine level were noted during the intra-arterial infusions. Metoprolol and propranolol decreased norepinephrine spillover and its rate of appearance in the forearm without affecting forearm blood flow. Isoprenaline and sodium nitroprusside increased and epinephrine decreased forearm norepinephrine spillover. Terbutaline increased forearm norepinephrine spillover and its rate of appearance in the forearm. Terbutaline increased the forearm rate of appearance and spillover of norepinephrine more than did sodium nitroprusside or isoprenaline at the same level of forearm blood flow. Infusion of isoprenaline failed to increase norepinephrine spillover or its forearm appearance rate more than would be expected from the increase in forearm blood flow. Administration of epinephrine increased spillover and forearm appearance rate of norepinephrine during intra-arterial infusion of yohimbine.ConclusionsThe terbutaline, propranolol, metoprolol and yohimbine plus epinephrine results suggest that β-adrenoceptors enhance release of norepinephrine from vascular sympathetic nerve endings in humans.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo clarify whether the acute and marked increase in blood pressure associated with smoking is accompanied by an alteration in arterial compliance.DesignArterial compliance was measured in 13 subjects before and after smoking a cigarette with a nicotine content of 1.2mg, or before and after sham smoking. Measurements were obtained with the subjects at rest and after prolonged brachial artery occlusion (12min).MethodsCompliance was measured using an echo-tracking system capable of continuously providing (300 readings/s) radial diameter data and, with the addition of a photoplesythmographic device, blood pressure measurement.ResultsAcute cigarette smoking caused a pressor and tachycardie response, and decreased markedly both resting radial artery diameter and compliance, at blood pressure values identical to those before smoking. The marked increase in radial artery diameter and compliance brought about by local ischaemia was unaffected by smoking, and no changes were observed both at rest and after ischaemia as a result of sham smoking.ConclusionsSmoking causes a marked reduction in radial artery compliance, and the effect is independent of the increase in blood pressure. However, the marked increase in compliance due to ischaemia is not modified by smoking.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

ObjectiveTo assess the circadian blood pressure profile observed 3 months after endarterectomy.DesignTwenty-five patients undergoing unilateral or bilateral carotid endarterectomy were compared with a control population of 20 patients, matched for age, sex, weight and drug therapy. Casual mean blood pressure measured by mercury sphygmomanometry was similar in both groups.ResultsNon-invasive ambulatory blood pressure monitoring showed that, whereas mean arterial pressure was identical in both groups, the group undergoing surgery had a significant increase in pulse pressure and its variability over 24 h. Such abnormalities predominated during the nocturnal period, in which the reduction in systolic blood pressure was less pronounced in the operated group than in controls. For all parameters there was no significant difference between subjects with unilateral or bilateral endarterectomy.ConclusionThis study provides evidence that patients with carotid endarterectomy were characterized in the long term by an increase in the pulsatile component of blood pressure and its variability, in association with a disturbance in the physiological circadian rhythm. Such findings were not identified using casual blood pressure measurements.

ISSN:0263-6352    

出版商:OVID    

年代:1994

数据来源: OVID