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8 August 2018 Testosterone plays a permissive role in angiotensin II-induced hypertension and cardiac hypertrophy in male rats
Jay S. Mishra, Amar S. More, Kathirvel Gopalakrishnan, Sathish Kumar
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Abstract

Sex hormones contribute to sex differences in blood pressure. Inappropriate activation of the renin-angiotensin system is involved in vascular dysfunction and hypertension. This study evaluated the role of androgens (testosterone) in angiotensin II (Ang II)-induced increase in blood pressure, vascular reactivity, and cardiac hypertrophy. Eight-week-old male Wistar rats underwent sham operation, castration, or castration with testosterone replacement. After 12 weeks of chronic changes in androgen status, Ang II (120 ng/kg per minute) or saline was infused for 28 days via subcutaneous miniosmotic pump, and changes in blood pressure was measured. Vascular reactivity and Ang II receptor levels were examined in mesenteric arteries. Heart weight, cardiac ANP mRNA levels, and fibrosis were also assessed. Ang II infusion increased arterial pressure in intact males. The Ang II-induced increase in hypertensive response was prevented in castrated males. Testosterone replacement in castrated males restored Ang II-induced hypertensive responses. Castration reduced vascular AT1R/AT2R ratio, an effect that was reversed by testosterone replacement. Ang II-induced hypertension was associated with increased contractile response of mesenteric arteries to Ang II and phenylephrine in intact and testosterone-replaced castrated males; these increases were prevented in castrated males. Ang II infusion induced increased left ventricle-to-body weight ratio and ANP mRNA expression, indicators of left ventricular hypertrophy, and fibrosis in intact and testosterone-replaced castrated males, and castration prevented the increase in these parameters caused by Ang II. This study demonstrates that testosterone plays a permissive role in development and maintenance of Ang II-induced vascular dysfunction, hypertension, and cardiac hypertrophy.

Summary Sentence

Testosterone, at physiologically relevant concentrations, plays a permissive role in development and maintenance of Ang II-induced hypertension, cardiac hypertrophy, and fibrosis via heightened angiotensin II receptor-mediated signaling.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Jay S. Mishra, Amar S. More, Kathirvel Gopalakrishnan, and Sathish Kumar "Testosterone plays a permissive role in angiotensin II-induced hypertension and cardiac hypertrophy in male rats," Biology of Reproduction 100(1), 139-148, (8 August 2018). https://doi.org/10.1093/biolre/ioy179
Received: 25 June 2018; Accepted: 7 August 2018; Published: 8 August 2018
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KEYWORDS
Angiotensin II
angiotensin receptors
blood pressure
gonadal steroids
hormone action
hypertrophy
mesenteric arteries
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