Cardiovascular protection by oestrogen—a calcium antagonist effect?

Collins, Peter; Rosano, Giuseppe; Jiang, Canwen; Lindsay, David; Poole-Wilson, P. A.; Sarrel, P.M.

doi:10.1016/0140-6736(93)91158-i

Cited by 258 publications

(88 citation statements)

References 14 publications

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“…24 -26 The results are also in agreement with experimental data that have shown that estrogen causes vascular relaxation in constricted blood vessels such as rabbit coronary artery 10,12 and human coronary artery. 27 We have also found that both progesterone and testosterone cause significant relaxation of the coronary artery, although the inhibitory effect of these hormones was less potent than that of 17␤-estradiol. Our results with progesterone are different from other reports, which have shown that progesterone induces a negative or opposing effect on blood flow and vasodilation and a minimal effect on canine coronary artery relaxation.…”

Section: Discussionmentioning

confidence: 87%

Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca ²⁺ Entry Mechanisms of Coronary Vasoconstriction

Crews

Khalil

1999

ATVB

153

185

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Abstract-The clinical observation that coronary artery disease is more common in men and postmenopausal women than in premenopausal women has suggested cardioprotective effects of female sex hormones including hormone-mediated coronary vasodilation. The purpose of this study was to investigate whether the sex hormone-induced coronary relaxation is caused by inhibition of Ca 2ϩ mobilization into coronary smooth muscle. Key Words: sex hormones Ⅲ calcium Ⅲ coronary Ⅲ contraction C oronary artery disease is one of the most common and costly diseases. Coronary vasospasm and subsequent occlusion are frequently associated with increased cardiovascular risk and may lead to myocardial infraction and death. 1 Clinical data suggest that the incidence of coronary heart disease is greater in men and postmenopausal women compared with premenopausal women. This is believed to be because of putative cardioprotective effects of the female sex hormone estrogen. The cardioprotective effects of estrogen have been explained by several mechanisms, including modification of lipid and carbohydrate metabolism, 2 modification of the composition of circulating lipoproteins, 3-5 and changes in blood coagulation, 6 as well as direct cardiovascular protective effects on hemodynamics. 7 Estrogens are vasodilators. For example, it has been reported that subcutaneous administration of ␤-estradiol in female guinea pigs reversibly and significantly lowers both the resting systolic blood pressure and the peak systolic blood pressure induced by a pressor challenge of norepinephrine. 8 Also intravenous infusion of estrogen in ovariectomized nonpregnant sheep has been shown to cause a significant increase in cardiac output and a decrease in systemic vascular resistance whereas local application of estrogen to the uterine artery only causes uterine vasodilation and increased uterine blood flow. 9 The vasodilator effects of estrogen have also been observed in normal coronary arteries. 10 The vascular endothelium has been suggested to play a role in mediating the estrogen-induced vasodilation. However, indomethacin does not affect the 17␤-estradiol-induced relaxation in endothelium-intact coronary arteries, 10 indicating that the release of vasodilator prostanoids is not involved in the 17␤-estradiol-induced coronary relaxation in vitro. Furthermore, estrogen causes vasodilation in deendothelialized rabbit coronary artery precontracted by endothelin-1, prostaglandin F 2␣ (PGF 2␣ ), and high-potassium depolarizing solution 10 suggesting that the estrogen-induced inhibition of vascular tone has an endothelium-independent component that involves direct action on vascular smooth muscle. 5,11,12

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Section: Discussionmentioning

confidence: 87%

Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca ²⁺ Entry Mechanisms of Coronary Vasoconstriction

Crews

Khalil

1999

ATVB

153

185

View full text Add to dashboard Cite

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“…For instance, a considerable body of data suggest that an important protective effect of estrogen is to potentiate the actions of endothelium-derived relaxing factors (13)(14)(15). Additionally, estrogen can enhance the effects of calcium channel blocking agents (16). Studies of the acute hemodynamic effects of estrogen have reported increases in cardiac output and peripheral blood flow in both humans and experimental animals (17).…”

Section: Introductionmentioning

confidence: 99%

Sex hormone modulation of serotonin-induced coronary vasodilation in isolated heart

Moysés

Barker

Cabral

2001

Braz J Med Biol Res

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The present study was designed to evaluate the differences in the coronary vasodilator actions of serotonin (5-HT) in isolated heart obtained from naive or castrated male and female rats that were treated with either estrogen or testosterone. Hearts from 12 groups of rats were used: male and female naive animals, castrated, castrated and treated with 17ß-estradiol (0.5 µg kg -1 day -1 ) for 7 or 30 days, and castrated and treated with testosterone (0.5 mg kg -1 day -1 ) for 7 or 30 days. After treatment, the vascular reactivity of the coronary bed was evaluated. Baseline coronary perfusion pressure (CPP) was determined and dose-response curves to 5-HT were generated. Baseline CPP differed between male (70 ± 6 mmHg, N = 10) and female (115 ± 6 mmHg, N = 12) naive rats. Maximal 5-HT-induced coronary vasodilation was higher (P<0.05) in naive female than in naive male rats. In both sexes, 5-HT produced endothelium-dependent coronary vasodilation. After castration, there was no significant difference in baseline CPP between hearts obtained from male and female rats (75 ± 7 mmHg, N = 8, and 83 ± 5 mmHg, N = 8, respectively). Castration reduced the 5-HT-induced maximal vasodilation in female and male rats (P<0.05). Estrogen treatment of castrated female rats restored (P<0.05) the vascular reactivity. In castrated male rats, 30 days of estrogen treatment increased (P<0.05) the responsiveness to 5-HT. The endothelium-dependent coronary vasodilator actions of 5-HT are greater in female rats and are modulated by estrogen. A knowledge of the mechanism of action of estrogen on coronary arteries could aid in the development of new therapeutic strategies and potentially decrease the incidence of cardiovascular disease in both sexes.

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“…In addition, almost nothing is known about the relationship between estrogen and EDHF. Additionally, estrogen can enhance calcium channel-blocking agents (16). Estrogen-induced relaxation may play an important role in the regulation of coronary tone and this may be one of the explanations of why estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women (17).…”

Section: Introductionmentioning

confidence: 99%

Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

Santos

Abreu

Bissoli

et al. 2004

Braz J Med Biol Res

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The present study was designed to determine relaxation in response to 17ß-estradiol by isolated perfused hearts from intact normotensive male and female rats as well as the contribution of endothelium and its relaxing factors to this action. Baseline coronary perfusion pressure was determined and the vasoactive effects of 17ß-estradiol (10 µM) were assessed by in bolus administration before and after endothelium denudation by infusion of 0.25 µM sodium deoxycholate or perfusion with 100 µM L-NAME, 2.8 µM indomethacin, 0.75 µM clotrimazole, 100 µM L-NAME plus 2.8 µM indomethacin, and 100 µM L-NAME plus 0.75 µM clotrimazole. Baseline coronary perfusion pressure differed significantly between males (84 ± 2 mmHg, N = 61) and females (102 ± 2 mmHg, N = 61). Bolus injection of 10 µM 17ß-estradiol elicited a transient relaxing response in all groups, which was greater in coronary beds from females. For both sexes, the relaxing response to 17ß-estradiol was at least in part endothelium-dependent. In the presence of the nitric oxide synthase inhibitor L-NAME, the relaxing response to 17ß-estradiol was reduced only in females. Nevertheless, in the presence of indomethacin, a cyclooxygenase inhibitor, or clotrimazole, a cytochrome P450 inhibitor, the 17ß-estradiol response was significantly reduced in both groups. In addition, combined treatment with L-NAME plus indomethacin or L-NAME plus clotrimazole also reduced the 17ß-estradiol response in both groups. These results indicate the importance of prostacyclin and endothelium-derived hyperpolarizing factor in the relaxing response to 17ß-estradiol. 17ß-estradiol-induced relaxation may play an important role in the regulation of coronary tone and this may be one of the reasons why estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women.

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Cardiovascular protection by oestrogen—a calcium antagonist effect?

Cited by 258 publications

References 14 publications

Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca ²⁺ Entry Mechanisms of Coronary Vasoconstriction

Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca ²⁺ Entry Mechanisms of Coronary Vasoconstriction

Sex hormone modulation of serotonin-induced coronary vasodilation in isolated heart

Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

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Cardiovascular protection by oestrogen—a calcium antagonist effect?

Cited by 258 publications

References 14 publications

Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca 2+ Entry Mechanisms of Coronary Vasoconstriction

Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca 2+ Entry Mechanisms of Coronary Vasoconstriction

Sex hormone modulation of serotonin-induced coronary vasodilation in isolated heart

Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

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Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca ²⁺ Entry Mechanisms of Coronary Vasoconstriction

Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca ²⁺ Entry Mechanisms of Coronary Vasoconstriction