Cited by 414Hormonal and reproductive studiesNitric Oxide and Endothelin EffectsEstrogen and related hormone effects

Testosterone Relaxes Rabbit Coronary Arteries and Aorta

Yue, Ping, Chatterjee, Kanu, Beale, Carolyn, Poole-Wilson, Philip A., Collins, Peter·1995·Circulation

Abstract

Background Until menopause, women appear to be protected from coronary heart disease. Evidence suggests that estrogen may play a role in the protection of the cardiovascular system by exerting a beneficial effect on risk factors such as cholesterol metabolism and by a direct effect on the coronary arteries. To date there has been no evidence linking testosterone with the occurrence of coronary heart disease. Testosterone may affect the cardiovascular system directly, thus partially explaining the difference in the incidence of coronary artery disease in men and premenopausal women. The purpose of this study was to assess the direct effect of testosterone and a number of testosterone analogues on rabbit coronary arteries and aorta in vitro. Methods and Results Rings of coronary artery and aorta of adult male or nonpregnant female New Zealand White rabbits were suspended in organ baths containing Krebs solution; isometric tension then was measured. The response to testosterone was investigated in prostaglandin F 2α (PGF 2α )- and KCl-contracted rings. The effects of endothelium and nitric oxide synthase, prostaglandin synthetase, and guanylate cyclase inhibition on testosterone-induced relaxation were investigated. The effects of ATP-sensitive potassium channels and potassium conductance were also assessed. Relaxing responses in the presence of aromatase inhibition and testosterone receptor blockade were performed. The relaxing responses to the testosterone analogues etiocholan-3β-ol-17-one, epiandrosterone, 17β-hydroxy-5α-androst-1-en-3-one, androst-16-en-3-ol, and testosterone enanthanate were measured. Testosterone relaxed rabbit coronary arteries and aorta. There was no significant difference between the relaxation effect of testosterone with or without endothelium. Similar results were obtained from male and nonpregnant female rabbits. The relaxing response of testosterone in the coronary artery was significantly greater than in the aorta. The relaxing response of testosterone in the coronary artery was significantly reduced by the potassium channel inhibitor barium chloride but not by the ATP-sensitive potassium channel inhibitor glibenclamide. The relaxing response to testosterone was greater in PGF 2α -contracted rings compared with KCl-contracted rings. Inhibitors of nitric oxide synthase, prostaglandin synthetase, and guanylate cyclase did not affect relaxation induced by testosterone. Inhibition of aromatase and testosterone receptors did not affect relaxation. Testosterone did not shift the rabbit coronary arterial calcium concentration–dependent contraction curves, whereas verapamil did. There were, however, significant differences in the relaxing response to testosterone compared with testosterone analogues. Testosterone was the most potent relaxing agent, suggesting that there may be a structure-function relation in the relaxing response. Conclusions Testosterone induces endothelium-independent relaxation in isolated rabbit coronary artery and aorta, which is neither mediated by prostaglandin I 2 or cyclic GMP. Potassium conductance and potassium channels but not ATP-sensitive potassium channels may be involved partially in the mechanism of testosterone-induced relaxation. The in vitro relaxation is independent of sex and of a classic receptor. The coronary artery is significantly more sensitive to relaxation by testosterone than the aorta. Testosterone is a more potent relaxing agent of rabbit coronary artery than other testosterone analogues.

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Crossref · 10.1161/01.cir.91.4.1154

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Authors
Yue, P., Chatterjee, K., Beale, C., Poole-Wilson, P. A., & Collins, P.
Affiliations
University of California, San Francisco (US)
Venue
Circulation
Published
1995-02-15
Volume
91
Issue
4
Pages
1154-1160
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
OpenAlex
W2070681318
Cited by
414
References
40
Citations by year
2026: 1 · 2025: 8 · 2024: 1 · 2023: 5 · 2022: 11 · 2021: 8 · 2020: 13 · 2019: 9 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 9 · 2014: 11 · 2013: 11 · 2012: 22
FWCI
8.69
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
testosterone, coronary artery relaxation, aortic relaxation, coronary artery disease, sex differences in cardiovascular disease, estrogen cardioprotection, ATP-sensitive potassium channels, potassium conductance, prostaglandin F2alpha, nitric oxide synthase, guanylate cyclase, aromatase, testosterone receptor, verapamil, rabbit model, menopause
MeSH terms
Animals, Aorta, Coronary Vessels, Endothelium, Vascular, Female, Male, Muscle Contraction, Muscle Relaxation, Muscle, Smooth, Vascular, Rabbits, Testosterone, Potassium Channels, In Vitro Techniques

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