Endothelium‐independent relaxation of rabbit coronary artery by 17β‐oestradiol <i>in vitro</i>

Jiang, Canwen; Sarrel, Philip M.; Lindsay, David; Poole‐Wilson, Philip A.; Collins, Peter

doi:10.1111/j.1476-5381.1991.tb12545.x

Cited by 350 publications

(177 citation statements)

References 37 publications

(39 reference statements)

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“…In veins, 17␤-estradiol did not cause a direct relaxation of smooth muscle (rings without endothelium). On the contrary, 17␤-estradiol relaxes arterial smooth muscle by activation of K ϩ channels, inhibition of voltagegated Ca 2ϩ channels and increases in extrusion of intracellular Ca 2ϩ (21,25,42,59).…”

Section: Discussionmentioning

confidence: 99%

Acute effects of 17β-estradiol on femoral veins from adult gonadally intact and ovariectomized female pigs

Bracamonte

Jayachandran

Rud

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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endothelium; hyperpolarizing factor; nitric oxide; potassium channels OBSERVATIONAL AND EPIDEMIOLOGICAL studies suggest that oral hormone replacement therapy provides primary prevention of coronary artery disease in postmenopausal women while it also increases the risk of venous thrombosis (5,20, 23,40,49,54,55). The reasons for these apparent opposite effects on the arterial and venous systems are not known. Effects of estrogen (17␤-estradiol) on the arterial circulation are well characterized (35). For example, 17␤-estradiol has both genomic and nongenomic effects on arteries. Some of these effects include rapid and sustained production and release of endothelium-derived nitric oxide (NO), changes in activation of K ϩ and Ca 2ϩ channels, and regulation of intracellular Ca 2ϩ (12,13,36,37,42,45,59). However, it is unknown whether 17␤-estradiol could cause effects in veins as endothelial and vascular smooth muscle cells from veins have estrogen receptors (ER)-␣ (ER␣) and -␤ (ER␤) (22). Information is needed to begin to understand mechanisms of how estrogen treatment increases the risk of venous thrombosis. Therefore, the experiments were designed to determine the acute affects of 17␤-estradiol on femoral veins and whether or not these effects were modulated by the ovarian status of the animal with the use of ovariectomy (by laparoscopy) to mimic menopause. This study fills an important gap in the literature because the acute effects of 17␤-estradiol in arteries are well documented (35), but the effects of 17␤-estradiol on veins are unknown. METHODS Animals.Gonadally intact and ovariectomized (Ovx) female Yorkshire pigs (6 mo old, 110-120 kg) were used for these experiments. The external genitalia from gonadally intact females showed changes associated with an estrus cycle. Serum levels of estrogen from gonadally intact females range from 10 to 30 pg/ml and estrogen levels in Ovx females are below the sensitivity level of assay (4, 57). Uterine weight was used as a bioassay for the efficacy of surgery and was significantly less in Ovx females (51.3 Ϯ 7.8 g) compared with gonadally intact females (86.6 Ϯ 12.3 g). All pigs were fed twice a day with Lean Grow (Land O'Lakes Farmland Feed), given free access to water, and were housed at 22°C on a 12:12-h light-dark cycle.Protocol. Four weeks after ovariectomy, Ovx and agematched gonadally intact female pigs were anesthetized (ketamine and xylazine, 12 and 8 mg/kg, respectively), and the femoral veins were removed. The veins were placed immediately into cold modified Krebs-Ringer bicarbonate solution of the following composition (in mmol/l): 118.3 NaCl, 4.7 KCl, 2.5 CaCl 2, 1.2 MgSO4, 1.2 KH2PO4, 25.0 NaHCO3, 0.026 Ca 2ϩ disodium EDTA, and 11.1 dextrose. After the adventitia was trimmed, the veins were cut into rings ϳ4-5 mm long. Some rings were stored at Ϫ80°C for subsequent Western blotting to evaluate expression of ERs. Other rings were prepared for organ chamber experiments or immunohistochemistry.Organ chamber experiments. Rings with and without endothelium were ...

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Section: Discussionmentioning

confidence: 99%

Acute effects of 17β-estradiol on femoral veins from adult gonadally intact and ovariectomized female pigs

Bracamonte

Jayachandran

Rud

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…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). Nevertheless, the mechanisms underlying this action are unknown (18).…”

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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“…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.…”

mentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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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Endothelium‐independent relaxation of rabbit coronary artery by 17β‐oestradiol in vitro

Cited by 350 publications

References 37 publications

Acute effects of 17β-estradiol on femoral veins from adult gonadally intact and ovariectomized female pigs

Acute effects of 17β-estradiol on femoral veins from adult gonadally intact and ovariectomized female pigs

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

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

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Endothelium‐independent relaxation of rabbit coronary artery by 17β‐oestradiol in vitro

Cited by 350 publications

References 37 publications

Acute effects of 17β-estradiol on femoral veins from adult gonadally intact and ovariectomized female pigs

Acute effects of 17β-estradiol on femoral veins from adult gonadally intact and ovariectomized female pigs

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

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

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