Diminished β-Adrenoceptor-Mediated Relaxation of Arteries from Spontaneously Hypertensive Rats

Fujimoto, Seigo; Dohi, Yasuaki; Aoki, Kyuzo; Matsuda, Tomohiro

doi:10.1007/978-4-431-68090-1_17

Cited by 3 publications

(4 citation statements)

References 17 publications

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“…These observations are in agreement with earlier work showing that vascular relaxations in response to ␤-adrenergic stimulation and, more generally in response to stimuli involving the stimulation of adenylate cyclase, are reduced in SHR (2, 9, 18, 36). The ␤-adrenergic dysfunction appears early, preceding the development of hypertension, and was attributed with either a decrease in G protein G s (18,36) or an increase in G i function and/or expression (4). ␤-Adrenoceptor-mediated vasorelaxation in various vessels declines during maturation and aging (13,44).…”

Section: Discussionmentioning

confidence: 99%

Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats

Gomez

Schwendemann²,

Roger³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Gomez E, Schwendemann C, Roger S, Simonet S, Paysant J, Courchay C, Verbeuren TJ, Félétou M. Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats. Am J Physiol Heart Circ Physiol 295: H2198 -H2211, 2008. First published September 26, 2008 doi:10.1152/ajpheart.00507.2008.-In spontaneously hypertensive rat (SHR) aorta, prostacyclin is an endotheliumderived contracting factor contributing to the endothelial dysfunction. This study was designed to determine whether the impairment of the prostacyclin response is influenced by aging and whether such a dysfunction is observed in platelets. Isometric tension was measured in aortic rings, and aggregation was studied in platelet-rich plasma taken from 3-, 6-, and 15-mo-old Wistar-Kyoto rats (WKY) and SHR. In aorta from 3-and 6-mo-old WKY, prostacyclin and beraprost [prostacyclin receptor (IP) agonists] produced relaxations that were enhanced by Triplion (thromboxane-prostanoid receptor antagonist). In 15-mo-old WKY, the relaxations to beraprost were maintained, but not those to prostacyclin. In SHR aorta, prostacyclin or beraprost produced no or minor relaxations, which, in younger SHR, were enhanced by Triplion. In both strains, the relaxations were inhibited by CAY-10441 (IP receptor antagonist). The relaxations to forskolin and isoproterenol were reduced with aging. When compared with those of WKY, the relaxations to isoproterenol were reduced in 3-but not in 6-or 15-mo-old SHR, whereas those to forskolin were consistently diminished at any given age. Whatever the age, prostacyclin and beraprost produced CAY-10441-sensitive inhibitions of ADPinduced platelet aggregation. Both agonists were more potent in SHR than in WKY. Therefore, in platelets from WKY and SHR, the IP receptor-dependent antiaggregant response is functional and maintained during aging. In aorta from WKY those responses are reduced by aging and, in SHR, are already compromised at 3 mo. This dysfunction of the IP receptor is only partially explained by a general dysfunction of the adenylate cyclase pathway. smooth muscle; prostacyclin receptor; endothelium-derived contracting factors; endothelial dysfunction; spontaneously hypertensive rats; Wistar-Kyoto rats ENDOTHELIAL DYSFUNCTION IS a generic term that encompasses many different disorders (15). In the genetic model of spontaneously hypertensive rats (SHR), the endothelial dysfunction is attributed to the release of endothelium-derived contracting factors (EDCF) that counterbalances the effect of nitric oxide (NO) with no or minor alteration in the production of the latter (35). In response to acetylcholine, the endothelium-dependent contraction involves the production of reactive oxygen species, the activation of cyclooxygenase-1, the diffusion of EDCF, and the subsequent stimulation of thromboxane-prostanoid (TP) receptors on vascular smooth muscle. Since inhibitors of thromboxane synthase do not affect the endothelium-dependent contraction to acetylcholine, thromboxane A 2 is not the EDCF released by the muscarinic agonist ...

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Section: Discussionmentioning

confidence: 99%

Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats

Gomez

Schwendemann²,

Roger³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…This parallels the case of ␤-adrenoceptor-mediated arterial relaxation in SHR, which has been shown to be impaired not only at the established stage of hypertension 9 -11 but also at the prehypertensive stage. Fujimoto et al 6,7 and Cheng et al 8 showed that ␤-agonist-induced relaxation is impaired in conduit arteries, such as femoral arteries, superior mesenteric arteries, and aortae, from prehypertensive SHR. Our study, however, is distinct from these previous studies in that we compared electrical responses, (ie, isoproterenol-induced hyperpolarization) and that we focused on mesenteric resistance arteries, which are thought to play a pivotal role in determining total peripheral resistance in rats.…”

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confidence: 99%

“…6,7 On the other hand, information is limited regarding ␤-adrenoceptor-mediated hyperpolarization in hypertension. To the best of our knowledge, the only previous report on this topic, made by Stekiel et al, 1 demonstrated that in situ hyperpolarization to isoproterenol is impaired in arterioles from reduced renal mass hypertensive rats.…”

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confidence: 99%

Impaired β-Adrenergic Hyperpolarization in Arteries From Prehypertensive Spontaneously Hypertensive Rats

2001

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Abstract-Stimulation of ␤-adrenoceptors leads to vascular smooth muscle hyperpolarization, presumably through the ␤-adrenoceptors/Gs protein/adenylate cyclase/ATP-sensitive K ϩ -channels (KATP) signaling cascade, which may play an important role in the sympathetic control of membrane potential. ␤-Adrenoceptor-mediated hyperpolarization has been shown to be impaired in the established stage of experimental hypertension. The present study tested the hypothesis that ␤-adrenergic hyperpolarization may be defective before the development of hypertension in some forms of genetic hypertension. We evaluated ␤-adrenoceptor-mediated hyperpolarization using microelectrodes in mesenteric resistance arteries from 5-week-old, prehypertensive, spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Isoproterenol-induced hyperpolarization was significantly smaller in SHR than in WKY (10 Ϫ7 mol/L: Ϫ4.6Ϯ0.6 versus Ϫ7.8Ϯ0.8 mV, PϽ0.01; 10 Ϫ6 mol/L: Ϫ7.8Ϯ0.5 versus Ϫ9.8Ϯ0.6 mV, PϽ0.05; nϭ9). Furthermore, hyperpolarization to cholera toxin, a direct activator of Gs protein, was also impaired in SHR. On the other hand, hyperpolarization to forskolin, an adenylate cyclase activator, and to levcromakalim, a KATP opener, was comparable between groups. These findings suggest that ␤-adrenoceptor-mediated hyperpolarization is defective in SHR before the development of hypertension, presumably because of an abnormality at the Gs protein site. Considering the importance of membrane potential in the control of vascular tone, altered ␤-adrenergic control of membrane potential might play a role in the development of hypertension in SHR. Key Words: receptors, adrenergic Ⅲ membrane potentials Ⅲ hyperpolarization Ⅲ hypertension, genetic Ⅲ rats, spontaneously hypertensive S timulation of vascular ␤-adrenoceptors leads to smooth muscle hyperpolarization and relaxation, presumably through the ␤-adrenoceptors/Gs protein/adenylate cyclase/ cAMP signaling cascade. 1,2 We recently demonstrated that isoproterenol-induced hyperpolarization is mediated by the opening of ATP-sensitive K ϩ channels (KATP) in rat mesenteric resistance arteries, 2 which parallels the case of the canine saphenous veins, 3 and that this ␤-adrenergic hyperpolarization plays an important role in the sympathetic control of membrane potential by opposing ␣-adrenoceptor-mediated depolarization. 4 In view of the importance of membrane potential as a determinant of smooth muscle tone, 5 ␤-adrenoceptor-mediated hyperpolarization may play an important role in the control of vascular tone.␤-Adrenoceptor-mediated relaxation is impaired in arteries from hypertensive rats, 6 -11 and in some models, such an abnormality has been shown to precede the development of hypertension. 6,7 On the other hand, information is limited regarding ␤-adrenoceptor-mediated hyperpolarization in hypertension. To the best of our knowledge, the only previous report on this topic, made by Stekiel et al, 1 demonstrated that in situ hyperpolarization to isoproterenol is impaired in arterioles f...

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“…Prior to this observation, Fujimoto et al [120] demonstrated that β-adrenoceptor-mediated relaxation of arteries, in the same species, was diminished before and during development of HTN. The diminished relaxation may be because of defective hyperpolarization induced by these receptors [121] .…”

Section: Involvement Of the Autonomic Nervous Systemmentioning

confidence: 92%

Prehypertension: Underlying pathology and therapeutic options

Albarwani

Al-Siyabi

Tanira

2014

WJC

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Prehypertension (PHTN) is a global major health risk that subjects individuals to double the risk of cardiovascular disease (CVD) independent of progression to overt hypertension. Its prevalence rate varies considerably from country to country ranging between 21.9% and 52%. Many hypotheses are proposed to explain the underlying pathophysiology of PHTN. The most notable of these implicate the renin-angiotensin system (RAS) and vascular endothelium. However, other processes that involve reactive oxygen species, the inflammatory cytokines, prostglandins and C-reactive protein as well as the autonomic and central nervous systems are also suggested. Drugs affecting RAS have been shown to produce beneficial effects in prehypertensives though such was not unequivocal. On the other hand, drugs such as β-adrenoceptor blocking agents were not shown to be useful. Leading clinical guidelines suggest using dietary and lifestyle modifications as a first line interventional strategy to curb the progress of PHTN; however, other clinically respected views call for using drugs. This review provides an overview of the potential pathophysiological processes associated with PHTN, abridges current intervention strategies and suggests investigating the value of using the "Polypill" in prehypertensive subjects to ascertain its potential in delaying (or preventing) CVD associated with raised blood pressure in the presence of other risk factors.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Prehypertension; Renin-angiotensin system; Therapeutic lifestyle changes; Polypill Core tip: There is a current debate over the ideal means of intervening in prehypertension. Since it is the cardiovascular risk that constitute the basis for intervention in both prehypertension and hypertension, the review discusses the following points, that: (1) categorizing blood pressure levels is based on mere 20 mmHg brackets; hence this doctrine may be re-visited to include other cardiovascular risk factors to categorize patients regardless of their blood pressure level; (2) investigating the therapeutic potential of intervening in all pathophysiological processes associated with prehypertension; and (3) ascertaining the therapeutic value of the "Polypill" in prehypertensives as means of primary prevention.Albarwani S, Al-Siyabi S, Tanira MO. Prehypertension: Underlying pathology and therapeutic options.

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Diminished β-Adrenoceptor-Mediated Relaxation of Arteries from Spontaneously Hypertensive Rats

Cited by 3 publications

References 17 publications

Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats

Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats

Impaired β-Adrenergic Hyperpolarization in Arteries From Prehypertensive Spontaneously Hypertensive Rats

Prehypertension: Underlying pathology and therapeutic options

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