Acute effects of conjugated estrogens on coronary blood flow response to acetylcholine in men

Blumenthal, Roger S.; Heldman, Alan W.; Brinker, Jeffrey A.; Resar, Jon R.; Coombs, Vicki J.; Gloth, Sean T.; Gerstenblith, Gary; Reis, Steven E.

doi:10.1016/s0002-9149(97)00596-1

Cited by 68 publications

(50 citation statements)

References 21 publications

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“…The hormonal milieu of the present patients was completely different from that in patients in the studies cited above [18,19,24,25]. After the onset of either androgen deprivation therapy (PEP or orchidectomy), the plasma testosterone level decreases to the castrate level but, in addition, orchidectomy significantly lowers the plasma oestradiol level, whereas PEP increases it to a level of ≈ 20 times the original [26].…”

Section: P L a S M A O E S T R A D I O L L E V E L A N D L O W R I S contrasting

confidence: 63%

“…In addition, as oestradiol is produced in the vascular tissues, it has a direct local effect in an autocrine and paracrine manner [10,21] but also a greater systemic effect [22]. In men, the suppression of endogenous oestrogens with an aromatase inhibitor (anastrozole) resulted in a significant decrease in flowmediated brachial dilatation [23], and oestrogen acutely improved the impairment of coronary blood flow induced by acetylcholine or by cold [24,25].…”

Section: P L a S M A O E S T R A D I O L L E V E L A N D L O W R I S mentioning

confidence: 99%

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A high pretreatment plasma oestradiol level is associated with a low risk of acute myocardial infarction in parenteral oestrogen therapy for locally advanced prostate cancer

et al. 2007

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intramuscularly administered PEP (240 mg/ month) therapy. Each patient was followed until the end of the primary therapy (up to 10 years) or until the first AMI (lethal or not). RESULTSThe risk of AMI, when the PEP and orchidectomy groups were analysed together, was lower in patients with a high ppE2 level, and this risk was independent of the ppT level, pretreatment diseases, medication, age, performance status, disease stage or grade. In the PEP therapy group the risk of AMI was statistically significantly lower in patients with a high ppE2 level ( ≥ 93 pmol/L) than in those with a low ppE2 level ( < 93 pmol/L; risk ratio 0.28, 95% confidence interval 0.10-0.84, P = 0.022). There was no such difference in the orchidectomy group. The ppT level had no association with the risk of AMI. CONCLUSIONSA high ppE2 level is associated with a low risk of AMI in patients with locally advanced prostate cancer treated with PEP; there was no such association for ppT level. In the orchidectomy group the ppE2 or ppT level was not statistically significantly associated with the risk of AMI.

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Section: P L a S M A O E S T R A D I O L L E V E L A N D L O W R I S contrasting

confidence: 63%

Section: P L a S M A O E S T R A D I O L L E V E L A N D L O W R I S mentioning

confidence: 99%

A high pretreatment plasma oestradiol level is associated with a low risk of acute myocardial infarction in parenteral oestrogen therapy for locally advanced prostate cancer

et al. 2007

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“…In denuded rat aortic rings, there is no sex difference in E 2 -induced vasodilation (9), and E 2 -induced vasorelaxation is independent of sex in rat tail arteries (10). Effects of E 2 on vascular reactivity are also evident in human males, as clinical studies show an improvement in blood flow following infusion of conjugated equine estrogens or oral E 2 (2,17). Although males used in the current study were gonad intact, castration has no effect on the vasodilatory response to E 2 in rat aortic strips and tail arteries (6,10).…”

Section: Discussionmentioning

confidence: 99%

Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation

Lindsey

Silva

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Lindsey SH, da Silva AS, Silva MS, Chappell MC. Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation. Am J Physiol Endocrinol Metab 305: E113-E118, 2013. First published May 14, 2013 doi:10.1152/ajpendo.00649.2012.-Previously, we reported that chronic activation of the estrogen receptor GPR30 by its selective agonist G-1 decreases blood pressure in ovariectomized hypertensive mRen2.Lewis (mRen2) rats but not intact male littermates. Furthermore, G-1 relaxes female mesenteric resistance arteries via both endothelium-dependent and -independent mechanisms. Because of the lack of a blood pressure-lowering effect by G-1 in males and the potential influence of aging on estrogen receptor expression, we hypothesized that GPR30-dependent vasodilation and receptor expression are altered in males and aged females. Thus, we assessed the response to 17␤-estradiol or G-1 in mesenteric arteries obtained from 15-wk-old normotensive Lewis and hypertensive mRen2 females and males as well as 52-wkold Lewis females. Vasodilation to 17␤-estradiol (E 2) and G-1 was significantly attenuated in 15-wk-old Lewis and mRen2 males compared with age-matched females. Pretreatment of male vessels with the nitric oxide synthase inhibitor L-NAME had no significant effect on the estradiol or G-1 response. In aged females, E 2 and G-1 vasorelaxation was also significantly blunted; however, L-NAME essentially abolished the response. Associated with the reduced vascular responses, GPR30 expression in mesenteric arteries was approximately 50% lower in males and aged females compared with young females. We conclude that alterations in GPR30 expression and signaling may contribute to vascular dysfunction in aging females and a greater blood pressure in hypertensive males.

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“…Thus, more clinical studies are needed to confirm the beneficial effects of acute administration of estrogen in females, although we have demonstrated in canine hearts that estrogen limits myocardial infarction size resulting from coronary artery occlusion and reperfusion regardless of sex. 7 Blumenthal et al 30 demonstrated an improvement in coronary vasodilation in males with intravenous conjugated estrogen. However, Collins et al 31 have shown a lack of effect in male coronary arteries in response to acute loading of estrogen for low availability or activity of estrogen receptors in male tissues.…”

Section: Study Limitationsmentioning

confidence: 98%

Differential Role of K _ATP Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects

2003

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Background-We have demonstrated that estrogen can reduce myocardial injury in ischemia-reperfusion via activation of ATP-sensitive potassium (K ATP ) channels. We sought to determine whether the protective effect of estrogen extends to epicardial coronary artery with attenuated vasoconstriction in patients after angioplasty by activation of such channels. Methods and Results-The study was designed to prospectively investigate 41 consecutive patients scheduled for elective coronary angioplasty. Pretreatment with estrogen limited myocardial ischemia during coronary occlusion and attenuated postangioplasty coronary vasoconstriction at the dilated and distal segments. An inhibitor of K ATP channels, glibenclamide, did not affect coronary vasomotor response, although it abolished the beneficial effect of estrogen on myocardial ischemia. Patients to whom estrogen was administered after the second balloon deflation experienced a similar magnitude of myocardial ischemia as controls but showed significantly attenuated vasoconstriction compared with controls (Pϭ0.0001). Endothelin-1 levels from the great cardiac vein rose significantly from 1.9Ϯ0.4 to 3.1Ϯ0.6 pg/mL (Pϭ0.001) 15 minutes after angioplasty in the control group; this was attenuated after estrogen was administered. Significant correlation was found between the changes in coronary vasomotion of the dilated segment and endothelin-1 levels (rϭ0.65, PϽ0.0001). Conclusions-These results demonstrate that estrogen is protective against both myocardial ischemia and coronary vasoconstriction through different mechanisms. The myocardial effect of estrogen was abolished by glibenclamide, which suggests that the cardioprotective effect of estrogen may result from activation of K ATP channels. In contrast, estrogen-induced attenuated vasoconstriction is associated with an attenuated release of endothelin-1, independent of K ATP activation.

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Acute effects of conjugated estrogens on coronary blood flow response to acetylcholine in men

Cited by 68 publications

References 21 publications

A high pretreatment plasma oestradiol level is associated with a low risk of acute myocardial infarction in parenteral oestrogen therapy for locally advanced prostate cancer

A high pretreatment plasma oestradiol level is associated with a low risk of acute myocardial infarction in parenteral oestrogen therapy for locally advanced prostate cancer

Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation

Differential Role of K _ATP Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects

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Acute effects of conjugated estrogens on coronary blood flow response to acetylcholine in men

Cited by 68 publications

References 21 publications

A high pretreatment plasma oestradiol level is associated with a low risk of acute myocardial infarction in parenteral oestrogen therapy for locally advanced prostate cancer

A high pretreatment plasma oestradiol level is associated with a low risk of acute myocardial infarction in parenteral oestrogen therapy for locally advanced prostate cancer

Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation

Differential Role of K ATP Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects

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Product

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Differential Role of K _ATP Channels Activated by Conjugated Estrogens in the Regulation of Myocardial and Coronary Protective Effects