Mechanisms of 17 β‐oestradiol induced vasodilatation in isolated pressurized rat small arteries

Shaw, Linda; Taggart, Michael J.; Austin, Clare

doi:10.1038/sj.bjp.0703084

Cited by 70 publications

(63 citation statements)

References 69 publications

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“…Although there are numerous reports in the literature detailing the beneficial influence of estrogen replacement on the vasculature in young animals (4,10,14,41), to our knowledge this is the first study to examine the effects of estrogen supplementation on the coronary vasculature in female rats of an advanced age. The foremost finding of this study is that age reduces flow-induced, NO-mediated vasodilation of coronary arterioles of female rats, and estrogen replacement improves flow-induced dilation in coronary arterioles of old female rats, indicating a favorable coronary endothelial response to estrogen replacement in this aged population.…”

Section: Discussionmentioning

confidence: 99%

Estrogen replacement restores flow-induced vasodilation in coronary arterioles of aged and ovariectomized rats

LeBlanc

Reyes

Kang³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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October 7, 2009; doi:10.1152/ajpregu.00178.2009.-The risk for cardiovascular disease (CVD) increases with advancing age; however, the age at which CVD risk increases significantly is delayed by more than a decade in women compared with men. This cardioprotection, which women experience until menopause, is presumably due to the presence of ovarian hormones, in particular, estrogen. The purpose of this study was to determine how age and ovarian hormones affect flowinduced vasodilation in the coronary resistance vasculature. Coronary arterioles were isolated from young (6 mo), middle-aged (14 mo), and old (24 mo) intact, ovariectomized (OVX), and ovariectomized ϩ estrogen replaced (OVE) female Fischer-344 rats to assess flowinduced vasodilation. Advancing age impaired flow-induced dilation of coronary arterioles (young: 50 Ϯ 4 vs. old: 34 Ϯ 6; % relaxation). Ovariectomy reduced flow-induced dilation in arterioles from young females, and estrogen replacement restored vasodilation to flow. In aged females, flow-induced vasodilation of arterioles was unaltered by OVX; however, estrogen replacement improved flow-induced dilation by ϳ160%. The contribution of nitric oxide (NO) to flow-induced dilation, assessed by nitric oxide synthase (NOS) inhibition with N G -nitro-L-arginine methyl ester (L-NAME), declined with age. L-NAME did not alter flow-induced vasodilation in arterioles from OVX rats, regardless of age. In contrast, L-NAME reduced flowinduced vasodilation of arterioles from estrogen-replaced rats at all ages. These findings indicate that the age-induced decline of flowinduced, NO-mediated dilation in coronary arterioles of female rats is related, in part, to a loss of ovarian estrogen, and estrogen supplementation can improve flow-induced dilation, even at an advanced age.endothelial nitric oxide synthase; Akt; nitric oxide; ovariectomy THE RISK FOR CARDIOVASCULAR disease (CVD) and heart failure increase with advancing age; however, sexual dimorphism exists in the chronological development of these risks (22,47). Although the chronological rate of aging is independent of sex, mechanisms that regulate the cardiovascular system across the lifespan may differ dramatically between men and women. The risk for CVD in men begins to increase at approximately the same age that flow-mediated vasodilation begins to decline (5). Women also exhibit this age-related impairment of flow-mediated vasodilation; however, significant reduction of flow-mediated dilation becomes apparent at the age of menopause, more than a decade later than in men (5). The cardioprotection that women experience until menopause is presumably due to the presence of ovarian estrogen and results in a sex-related delay of the expression of CVD (49). Chronic estrogen treatment has been shown to enhance endothelial function in a number of vascular beds (27, 31, 39), in part, through a pathway involving activation of Akt/PKB and subsequent phosphorylation of endothelial nitric oxide synthase (eNOS) (3,10,15,43,44). Endothelium-dependent vasodilation to a...

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Section: Discussionmentioning

confidence: 99%

Estrogen replacement restores flow-induced vasodilation in coronary arterioles of aged and ovariectomized rats

LeBlanc

Reyes

Kang³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Like the body of experimental information regarding NO-related mechanisms, the results of some studies support a role for vasodilator prostanoids in the acute actions of estrogen (29,30), while others do not (25,27,31). Of some additional interest, many of the studies on peripheral vascular tissue, reporting prostanoid-and/ or NO-dependence, also found that the acute E2 response could be blocked by pretreatment with an estrogen receptor blocker (7, 14, 17 -19, 22).…”

Section: Estrogen and Vasodilationmentioning

confidence: 94%

“…Evidence for direct actions of estrogen on non-cerebral vascular smooth muscle has been obtained in isolated cell systems and in endotheliumdenuded vessel preparations. Some reports have revealed a stereoselective effect of estrogen (9,27,32) on vascular smooth muscle that may (9,32) or may not (25,27,33) involve classical estrogen receptors. Other publications point to direct vascular smooth muscle relaxant effects of estrogen that variously depend upon: a) increases in intracellular cAMP (9,26) or cGMP (26); b) activation of the cGMP-dependent kinase (34); c) potentiation of Ca…”

Section: Estrogen and Vasodilationmentioning

confidence: 99%

Estrogen and Cerebrovascular Physiology and Pathophysiology

Pelligrino

Galea

2001

Japanese Journal of Pharmacology

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ABSTRACT-Numerous studies have uncovered a wide variety of estrogen effects with apparent cardiovascular benefits, the most recognized ones being vasodilation, anti-atherogenesis, diminished post-ischemic inflammation and anti-oxidant effects. This article provides an overview of the influence of estrogen on the cerebral vasculature, under physiologic and pathophysiologic conditions, and covers both acute and chronic effects. The discussion is primarily focused on the vasodilatory and anti-inflammatory actions of estrogen, since those particular estrogen influences have received the greatest attention in studies published to date. With respect to vasodilation, although some consideration is given to the role of other vasodilating mechanisms and factors, the emphasis is mostly placed on the endothelial isoform of nitric oxide synthase, eNOS, which has emerged as a clear target of estrogen. Some consideration is given to recent findings that suggest that estrogen can stimulate eNOS activity by decreasing the expression of the eNOS inhibitor caveolin-1. With regard to the ability of estrogen to counteract inflammation, potential mechanisms by which estrogen limits the post-ischemic leukocyte adhesion, and the expression of the inducible NOS, are discussed.

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“…Estrogen receptors have been identified on both vascular endothelial (4,10) and smooth muscle cells (5,21,22,29), providing two potential pathways by which estrogen could affect vascular function. In addition, non-receptor-mediated mechanisms may play a role (35). Estrogen treatment has been reported to increase production of the vasodilator nitric oxide (8) but to decrease production of the inducible nitric oxide synthetase (38).…”

mentioning

confidence: 99%

Effects of sex and estrogen on myosin COOH-terminal isoforms and contractility in rat aorta

Rutgeerts

Bowman²,

Johnson³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Paul RJ, Bowman PS, Johnson J, Martin AF. Effects of sex and estrogen on myosin COOH-terminal isoforms and contractility in rat aorta. Am J Physiol Regul Integr Comp Physiol 292: R751-R757, 2007. First published August 17, 2006; doi:10.1152/ajpregu.00167.2006.-We reported that estrogen treatment of ovariectomized rats increased uterine smooth muscle contractility and the ratio of the COOH-terminal myosin heavy chain isoform SM1 (204 kDa) and SM2 [200 kDa; Hewett TE, Martin AF, Paul RJ. J Physiol (Lond) 460: 351-364, 1993]. We extended this model to study sex and estrogen effects on vascular contractility. Experimental groups included 10-to 14-wk-old male (M), female (F), ovariectomized female (OF), and OF treated with estrogen (OF&E) for 7 days with a subcutaneous pellet delivery system, resulting in 17␤-estradiol of 85 (OF&E) vs. 5 (OF or M) pg/ml. The SM1-to-SM2 ratio increased from 1.8 to 2.6 in thoracic aorta, similar to uterine muscle. Isometric force was measured in 5-mm segments of intact and endothelium-denuded (Ϫendo) aorta. With KCl, the maximum forces were in the order OF Ϸ M Ͼ OF&E, and ED50 OF&E Ͼ OF Ϸ M. Differences in ED50 with estrogen persisted after endothelial denudation. The decreased force in Ϫendo OF aorta was not seen in OF&E, suggesting that estrogen altered an endothelium-dependent effect. No differences in maximum forces were noted with norepinephrine: ED50 OF Ͼ OF&E Ͼ M. Estrogen treatment, in contrast to KCl, increased sensitivity. Endothelial denudation increased sensitivity but reduced the differences between groups. With ACh relaxation, males were more sensitive than females, and estrogen had no effect. In the abdominal aorta, there were no changes in SM1/SM2 with 17␤-estradiol, and differences in contractility were blunted. In summary, estrogen treatment decreased responses to KCl but increased sensitivity to norepinephrine; male rats always demonstrated the highest contractility. An increase in the COOH-terminal myosin heavy chain isoform SM1-to-SM2 ratio with 17␤-estradiol treatment may underlie the changes observed in contractility.estrogen; vascular sensitivity; isometric force; myosin isoforms; ovariectomy THE OCCURRENCE OF CARDIOVASCULAR diseases is greater in men aged 30 -50 yr compared with women of similar age (15, 16). The incidence of cardiovascular diseases is also greater in postmenopausal compared with premenopausal women, and vascular protective effects of female sex hormones have been proposed (15,16,18,31). Currently, estrogen replacement therapy to postmenopausal women is in widespread use, but its validity is questioned (14,17,23,27,34,36). The mechanism by which sex and/or estrogen may affect the heart is unknown; it is likely to be multifactorial and has been reviewed in detail (30, 40). Estrogen receptors have been identified on both vascular endothelial (4, 10) and smooth muscle cells (5, 21, 22, 29), providing two potential pathways by which estrogen could affect vascular function. In addition, non-receptor-mediated mechanisms may play a role (35). Estroge...

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Mechanisms of 17 β‐oestradiol induced vasodilatation in isolated pressurized rat small arteries

Cited by 70 publications

References 69 publications

Estrogen replacement restores flow-induced vasodilation in coronary arterioles of aged and ovariectomized rats

Estrogen replacement restores flow-induced vasodilation in coronary arterioles of aged and ovariectomized rats

Estrogen and Cerebrovascular Physiology and Pathophysiology

Effects of sex and estrogen on myosin COOH-terminal isoforms and contractility in rat aorta

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