17β-Estradiol Attenuates Acetylcholine-Induced Coronary Arterial Constriction in Women but Not Men With Coronary Heart Disease

Collins, Peter; Rosano, Giuseppe; Sarrel, Philip M.; Ulrich, Lian G.; Adamopoulos, Stamatis; Beale, Carolyn M.; McNeill, J.; Poole‐Wilson, Philip A.

doi:10.1161/01.cir.92.1.24

Cited by 483 publications

(197 citation statements)

References 41 publications

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“…The estrogen receptor ␤-deficient mice develop sustained systolic and diastolic hypertension, but only as they age (Ͼ6 months) (22). Estrogen reverses acetylcholineinduced vasoconstriction of coronary vessels, possibly via facilitation of endothelium-dependent relaxation (23), which may be mediated by an enhancement of NO production via stimulation of NO synthase (24). There is also a rapid nongenomic effect on endothelial cells leading to vasodilatation when estrogens are applied transdermally (25).…”

Section: Discussionmentioning

confidence: 99%

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Head

Obeyesekere

Jones³

et al. 2004

Endocrinology

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Aromatase-deficient (ArKO) mice are deficient in estrogens due to deletion of the aromatase gene. We hypothesized that there may be changes in the cardiovascular system of ArKO mice because of evidence linking estrogens with improved cardiovascular outcomes and the induction of the glucocorticoid-metabolizing enzyme, 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2), gene in the kidney, which is important for the regulation of blood pressure (BP). BP and baroreflex sensitivity (BRS) in female conscious ArKO mice were compared with those in age-and weight-matched wild-type (WT) mice. Power spectral analysis was used to determine cardiovascular variability and BRS. Although systolic BP was similar in the two groups, diastolic and mean BPs were lower in the ArKO mice (؊6.3 ؎ 1.9 and ؊4.6 ؎ 2.1 mm Hg, respectively).Heart rate (HR) was greater in the ArKO mice (؉36 ؎ 6 beats/ min). The mean BP in WT mice was 105 mm Hg, and the HR was 481 beats/min. In the autonomic frequency range, BP variability was 74% greater, and HR variability was only 26% that in WT mice. The BRS of ArKO mice was 46% of the value observed in WT mice. 11␤HSD2 levels were unaltered in ArKO mice, except in the kidney, where they were only 10% of WT levels. Estradiol administration to ArKO mice restored renal 11␤HSD2 to WT levels. The results show that ArKO mice have lower diastolic BP, but increased BP variability, perhaps due to an impaired BRS. Thus, aromatase activity is critical for normal autonomic control of the heart and, hence, for reducing the deleterious effects of high BP variability. (Endocrinology 145: 4286 -4291, 2004)

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Section: Discussionmentioning

confidence: 99%

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Head

Obeyesekere

Jones³

et al. 2004

Endocrinology

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“…Studies have documented that E2 can induce relaxation of coronary arteries, reverse acetylcholine-induced vasoconstriction and improve exercise-induced myocardial ischemia in women with coronary artery disease (29)(30)(31)(32). Collins et al (33) showed that E2 decreases acetylcholine-induced coronary artery responses only in women, but not in men. These vasodilatory effects of estrogen are largely believed to be mediated by increased synthesis and release of nitric oxide, a potent relaxant of vascular smooth muscle (34).…”

Section: Estrogen and Vascular Tonementioning

confidence: 99%

Estrogen replacement therapy and cardioprotection: mechanisms and controversies

Subbiah

2002

Braz J Med Biol Res

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Epidemiological and case-controlled studies suggest that estrogen replacement therapy might be beneficial in terms of primary prevention of coronary heart disease (CHD). This beneficial effect of estrogens was initially considered to be due to the reduction of low density lipoproteins (LDL) and to increases in high density lipoproteins (HDL). Recent studies have shown that estrogens protect against oxidative stress and decrease LDL oxidation. Estrogens have direct effects on the arterial tissue and modulate vascular reactivity through nitric oxide and prostaglandin synthesis. While many of the effects of estrogen on vascular tissue are believed to be mediated by estrogen receptors a and ß, there is evidence for immediate non-genomic effects. The role of HDL in interacting with 17ß-estradiol including its esterification and transfer of esterified estrogens to LDL is beginning to be elucidated. Despite the suggested positive effects of estrogens, two recent placebo-controlled clinical trials in women with CHD did not detect any beneficial effects on overall coronary events with estrogen therapy. In fact, there was an increase in CHD events in some women. Mutations in thrombogenic genes (factor V Leiden, prothrombin mutation, etc.) in a subset of women may play a role in this unexpected finding. Thus, the cardioprotective effect of estrogens appears to be more complicated than originally thought and requires more research.

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“…8 There may be a direct effect on the vessel wall where steroid receptors are known to exist, 9 and testosterone infused into coronary arteries in men with coronary artery disease causes vasodilatation. 10 Infusion of oestradiol does not seem to cause relaxation of male coronary arteries, 11 so fall in oestradiol levels is unlikely to be responsible for the effects on arterial compliance we observed. There may be interaction through insulin pathways as testosterone replacement in middleaged obese men improves insulin sensitivity.…”

Section: Discussionmentioning

confidence: 72%

Androgen deprivation in males is associated with decreased central arterial compliance and reduced central systolic blood pressure

et al. 2000

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The higher incidence of coronary artery disease in men is often attributed to androgens. Arterial compliance or 'stiffness' is increasingly regarded as a modifiable risk factor for cardiovascular disease. We wanted to look at the effects of complete androgen withdrawal, on arterial compliance in men. We performed arterial compliance studies on 12 men with complete androgen deprivation as treatment for prostate cancer, and on 12 agematched healthy controls. Central pulse wave velocities were significantly higher in the androgen-deprived men (14.2 ؎ 2.7 vs 11.8 ؎ 1.6 m/sec, P ‫؍‬ 0.02). The cases

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17β-Estradiol Attenuates Acetylcholine-Induced Coronary Arterial Constriction in Women but Not Men With Coronary Heart Disease

Cited by 483 publications

References 41 publications

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Estrogen replacement therapy and cardioprotection: mechanisms and controversies

Androgen deprivation in males is associated with decreased central arterial compliance and reduced central systolic blood pressure

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