Comparable vasorelaxant effects of 17α- and 17β-oestradiol on rat mesenteric resistance arteries: an action independent of the oestrogen receptor

Naderali, Ebrahim K.; WALKER, Adrian B.; DOYLE, Patrick; Williams, Gareth

doi:10.1042/cs19990162

Cited by 9 publications

(11 citation statements)

References 38 publications

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“…This reduced sensitivity to E 2 in larger arteries is in agreement with findings of others (Lindsey et al 2011). Furthermore, the differential sensitivities to E 2 of the mesenteric, renal, and uterine arteries observed in this study are similar to values reported by others (Naderali et al 1999, Leung et al 2005, Scott et al 2007 Previous studies have shown that in vivo administration of the nonselective ER antagonist ICI 182 780 into one uterine artery of ovariectomized and E 2 -treated nonpregnant sheep blunted the E 2 effect on uterine blood flow, confirming its ER dependence (Magness et al 2005). Here, we show that ICI 182 780 resulted in a significant rightward shift in the CRCs to E 4 and E 2 , suggesting the contribution of ER.…”

Section: Discussionsupporting

confidence: 83%

Vasorelaxing effects of estetrol in rat arteries

Hilgers¹,

Oparil²,

Wouters³

et al. 2012

Journal of Endocrinology

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This study compared ex vivo relaxing responses to the naturally occurring human hormone estetrol (E 4 ) vs 17b-estradiol (E 2 ) in eight different vascular beds. Arteries were mounted in a myograph, contracted with either phenylephrine or serotonin, and cumulative concentrationresponse curves (CRCs) to E 4 and E 2 (0 . 1-100 mmol/l) were constructed. In all arteries tested, E 4 had lower potency than E 2 , although the differential effect was less in larger than smaller arteries. In uterine arteries, the nonselective estrogen receptor (ER) blocker ICI 182 780 (1 mmol/l) caused a significant rightward shift in the CRC to both E 4 and E 2 , indicating that the relaxation responses were ER dependent. Pharmacological blockade of nitric oxide (NO) synthases by N u -nitro-L-arginine methyl ester (L-NAME) blunted E 2 -mediated but not E 4 -mediated relaxing responses, while inhibition of prostaglandins and endothelium-dependent hyperpolarization did not alter relaxation to either E 4 or E 2 in uterine arteries. Combined blockade of NO release and action with L-NAME and the soluble guanylate cyclase (sGC) inhibitor ODQ resulted in greater inhibition of the relaxation response to E 4 compared with E 2 in uterine arteries. Endothelium denudation inhibited responses to both E 4 and E 2 , while E 4 and E 2 concentration-dependently blocked smooth muscle cell Ca 2C entry in K C -depolarized and Ca 2C -depleted uterine arteries. In conclusion, E 4 relaxes precontracted rat arteries in an artery-specific fashion. In uterine arteries, E 4 -induced relaxations are partially mediated via an endothelium-dependent mechanism involving ERs, sGC, and inhibition of smooth muscle cell Ca 2C entry, but not NO synthases or endothelium-dependent hyperpolarization.

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Section: Discussionsupporting

confidence: 83%

Vasorelaxing effects of estetrol in rat arteries

Hilgers¹,

Oparil²,

Wouters³

et al. 2012

Journal of Endocrinology

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“…To exclude possible vascular effects of ethanol, two arteries from each animal in each experiment were studied in the presence of the same volume of ethanol as the test arteries. As reported previously, there was no significant effect of this low concentration of ethanol on contractility induced by either KPSS or NA [29,30].…”

Section: Reagentssupporting

confidence: 70%

The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean and obese rats

Naderali¹,

SMITH²,

DOYLE³

et al. 2001

Clinical Science

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Resveratrol has been shown to induce vasorelaxation. In this study, we investigated the mechanism(s) of resveratrol-induced vasorelaxation in resistance mesenteric arteries from male lean and dietary-induced obese rats. Compared with lean rats, arteries from dietary-obese rats showed significant (P<0.001) endothelial dysfunction, as indicated by a decrease (>20%) in maximal acetylcholine-induced vasorelaxation. Resveratrol (5-35 micromol/l) induced concentration-dependent relaxation of mesenteric arteries preconstricted with noradrenaline (8 micromol/l) or KCl (125 mmol/l) from both lean and dietary-obese rats. There were no significant differences between the two groups, achieving a maximum relaxation of >95% at a concentration of 35 micromol/l. In noradrenaline-preconstricted arteries from lean rats, N(G)-nitro-L-arginine methyl ester (L-NAME; 100 and 300 micromol/l) caused a significant (P<0.01) concentration-dependent rightward shift in reseveratrol activity, with no effect on maximal responses. However, L-NAME (100 and 300 micromol/l) did not alter the effects of reseveratrol on arteries from dietary-obese rats, giving superimposed concentration-responses curves. Indomethacin was also ineffective in altering resveratrol activity in arteries from both lean and dietary-obese rats. In noradrenaline-precontracted arteries from dietary-obese rats, responses to resveratrol were not attenuated by endothelial denudation, indicating an action independent of the endothelium. This study indicates that: (a) the maximal effects of resveratrol on resistance arteries from lean and dietary-obese rats are not effected by endothelial dysfunction, and (b) the effects of resveratrol in lean animals (where endothelial function is not impaired), but not in dietary-obese rats, are mediated via NO.

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“…literature. Indeed, some laboratories have reported that 17␣-E 2 relaxed pig coronary arteries without achieving complete dilatation when contracted with Ca 2ϩ (34), while others noted that 17␣-E 2 generated relaxation similar to that of 17␤-E 2 in the mesenteric arteries of rats (26). On the other hand, 17␣-E 2 displayed only minor effects on mesenteric artery diameter over a concentration range similar to the effective vasodilatory concentration of 17␤-E 2 in the same strain of rats (37).…”

Section: Discussionmentioning

confidence: 90%

Vasorelaxant action of 17β-estradiol in rat uterine arteries: role of nitric oxide synthases and estrogen receptors

Scott

Tremblay²,

Brochu³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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The uterine vasculature plays an important role during pregnancy by providing adequate perfusion of the maternal-fetal interface. To this end, substantial remodeling of the uterine vasculature occurs with consequent changes in responsiveness to contractile agents. The purpose of our study was to characterize the vasorelaxant effects of estrogens on vascular smooth muscles of the rat uterine artery during pregnancy and to evaluate the involvement of estrogen receptors (ESR) and nitric oxide synthases (NOS). To do so, we measured NOS expression in the whole uterine and mesenteric circulatory bed by Western blotting. Vasorelaxant effects of 17beta-estradiol (17beta-E(2)) were assessed on endothelium-denuded uterine arteries with wire myographs in the absence and presence of pharmacological modulators [nitro-L-arginine methyl ester (L-NAME), ICI-182780, tamoxifen]. All experiments were performed on arteries from nonpregnant (NP) and late pregnant (P) rats. In the uterine vasculature of the latter group, NOS3 (endothelial NOS) expression was increased, while NOS1 (neuronal NOS) was reduced compared with NP rats. Expression of the NOS2 (inducible NOS) isoform was undetectable in the two groups. Both 17beta-E(2) and 17alpha-E(2) induced uterine artery relaxation, but the latter evoked lower responses. Endothelium-denuded arteries from NP rats showed larger relaxation with 17beta-E(2) than P rats. This larger relaxation disappeared in the presence of L-NAME. The ESR antagonist ICI-182780 did not affect acute relaxation with 17beta-E(2) and 17alpha-E(2). Moreover, membrane-nonpermeant 17beta-E(2):BSA (estradiol conjugated to bovine serum albumin) did not induce any vasorelaxation. Our results indicate that estrogens exert direct acute vasorelaxant effects in smooth muscles of the rat uterine artery that are mediated by mechanisms independent of ESR activation, but with some stereospecificity. Part of this effect, in NP rats only, is due to nitric oxide produced from muscle NOS1.

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Comparable vasorelaxant effects of 17α- and 17β-oestradiol on rat mesenteric resistance arteries: an action independent of the oestrogen receptor

Cited by 9 publications

References 38 publications

Vasorelaxing effects of estetrol in rat arteries

Vasorelaxing effects of estetrol in rat arteries

The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean and obese rats

Vasorelaxant action of 17β-estradiol in rat uterine arteries: role of nitric oxide synthases and estrogen receptors

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