摘要:

Abstract:Recent years have witnessed astonishing progress in our understanding of the molecular basis of adrenoceptor structure, function and regulation and revealed an unexpected heterogeneity of adrenoceptors demonstrating the existence of at least 11 subtypes. This paper discusses the implications of these advances on studies regarding a specific role of adrenoceptors in the development of genetic hypertension. The available data indicate that among the α‐adrenoceptor subtypes the α2A‐adrenoceptor is the most likely candidate for an alteration specifically linked to genetic hypertension in the animal model of the spontaneously hypertensive rat and possibly in some patients. Alterations of other α‐adrenoceptor subtypes may be specific for some forms of genetic hypertension but are unlikely to play an important role for blood pressure regulation. Most β‐adrenoceptor alterations appear to occur secondary to blood pressure elevation independently of whether hypertension has occured on a genetic basis or not. Moreover, the mechanisms regulating α‐ and β‐adrenoceptor responsiveness upon prolonged agonist exposure may be altered in hypertension and thereby contribute to the pathophysiolog

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb01615.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb01616.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:The possible role of 5‐hydroxytryptamine (5HT) and 5HT‐receptors in hypertension, already suggested by Page in 1954, has been subject to a renaissance of interest owing to the development of antihypertensive drugs which interact with 5HT‐receptors. These drugs, like ketanserin, urapidil and flesinoxan are used as tools to study the role of 5HT and its receptors in hypertension. Some arguments would plead in favour of a certain role of 5HT and 5HT‐receptors in the pathogenesis and maintenance of hypertension: hyperresponsiveness of blood vessels from hypertensive patients and animals to 5HT‐induced constriction; the antihypertensive/vasodilator activity of the 5HT2‐receptor antagonist ketanserin; enhanced sensitivity of platelets from hypertensives to 5HT. However, there are also several arguments which do not support a causal role of 5HT in hypertensive disease: 5HT is not a generally accepted pressor agent, whereas its concentration in the circulating blood is subthreshold; the 5HT2‐receptor antagonist ketanserin is the only agent of this type which lowers blood pressure, other 5HT2‐receptor blockers (ritanserin; LY 53587) being inactive. The various data and arguments available do not unequivocally support a relevant role of peripheral 5HT and its receptors in hypertensive disease. 5HT2‐receptor blockade may, however, have a favourable effect on the microcirculation under pathological conditions. The stimulation of central 5HT1A‐receptors by drugs like urapidil, 8‐OH‐DPAT or flesinoxan, has been demonstrated to induce peripheral sympathoinhibition and a fall in blood pressure. This mechanism appears to be a novel target for centrally acting antihypertensives, clearly different from that of clonidine and related drugs, which are centrally acting

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb01617.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb01618.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Alterations in neurohormonal response are a widely‐observed feature in various forms of hypertension. Such responses depend not only on levels of hormones/neurotransmitters, but also on receptors and post‐receptor components. With respect to G protein‐coupled receptors, such as those for catecholamines, angiotensin II, and bradykinin, it is possible that G‐proteins or G protein‐coupled effector molecules are altered in hypertension. In this article, several classes of Gαproteins and effectors which link to these proteins are briefly discussed. Evidence is presented in support of the concept that signal amplification in G protein‐coupled receptor systems occurs at the level of receptor activation of the G proteins. Limited data are as yet available that directly assess whether changes in the amount or properties of particular Gαproteins or G‐protein‐linked effectors, are altered in hypertension. The availability of antibody, cDNA and other genetic probes should prove highly useful in testing the hypothesis that such alterations are important for the pathogenesis and maintenance of the h

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb01619.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium‐derived vasoactive substances are nitric oxide, prostacyclin, endothelin‐1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension and hypercholesterolaemia. All three conditions are associated with a decreased basal and stimulated release of endothelium‐derived nitric oxide. On the other hand, the release of endothelin‐1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of a cyclooxygenase‐dependent endothelium‐derived contracting factor, most likely prostaglandin H2. The circulating levels of endothelin‐1 on the other hand are not increased in experimental and human hypertension. In the porcine coronary circulation, oxidized low‐density lipoproteins selectively reduce endothelium‐dependent relaxations to aggregating platelets, serotonin and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension and hypercholesterolaemia may have important clinical implications for the pathogenesis of cardi

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb01620.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb01622.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1992.tb01614.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY