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Antihypertensive effects of androgens in conscious, spontaneously hypertensive rats.
J Steroid Biochem Mol Biol 2017; 167:106-114JS

Abstract

Androgens are vasoactive steroids that induce acute vasodilation in a number of isolated vascular beds from different species, but the effects of these hormones on systemic blood pressure (BP) have been studied little. Although it has been reported that androgens exert systemic hypotensive effects through peripheral vasodilation in normotensive rats, there have not been any reports of systemic hypotensive effects of androgens in animals with hypertension. This study was designed to evaluate the acute effects of testosterone (TES) and its 5-reduced metabolites on systemic BP in hypertensive rats and to test the hypothesis that hypotestosteronemia may be involved in the pathogenesis of hypertension. Chronic, indwelling catheters were implanted in carotid artery and jugular vein of 18-21-week-old male spontaneously hypertensive rats (SHR) and normotensive-control Wistar-Kyoto (WKY) rats, for BP recording and drug administration, respectively. Bolus injections of TES, 5α- or 5β-dihydrotestosterone (5α- and 5β-DHT), were administrated cumulatively to conscious rats at doses of 0.1-100μmolkg-1min-1. 5β-DHT was also administrated during the pressor effect of Bay K 8644, an L-type voltage-operated Ca2+ channel (L-VOCC) agonist. In separate experiments, BP of orchidectomized normotensive male WKY and Wistar rats, with or without androgen-replacement therapy, was evaluated weekly for 10 weeks by tail-cuff plethysmography. TES and its metabolites reduced BP in a dose-dependent manner, while heart rate was reduced with some androgens at the highest doses. The hypotensive effects of androgens were markedly greater in SHR, with a rank order potency of: 5β-DHT>TES>5α-DHT. 5β-DHT, the most potent antihypertensive androgen, abolished the pressor response to Bay K 8644 in SHR. TES deprivation by orchidectomy increased BP in normotensive WKY and Wistar rats, but this hypertension was prevented by TES replacement therapy. BP responses to androgens are androgen structure-dependent. These data indicate that: 1) androgens play a significant role in the control of BP and may contribute to the pathogenesis of hypertension; 2) blockade of L-VOCC is involved in the antihypertensive effects of androgens, which are non-genomically mediated; and 3) hypotestosteronemia may be a risk factor for hypertension.

Authors+Show Affiliations

Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, México City 04510, Mexico. Electronic address: perusqui@unam.mx.Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, México City 04510, Mexico.Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain; Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.Women's Health Division, Michael E. DeBakey Institute, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466, USA; Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27888135

Citation

Perusquía, Mercedes, et al. "Antihypertensive Effects of Androgens in Conscious, Spontaneously Hypertensive Rats." The Journal of Steroid Biochemistry and Molecular Biology, vol. 167, 2017, pp. 106-114.
Perusquía M, Herrera N, Ferrer M, et al. Antihypertensive effects of androgens in conscious, spontaneously hypertensive rats. J Steroid Biochem Mol Biol. 2017;167:106-114.
Perusquía, M., Herrera, N., Ferrer, M., & Stallone, J. N. (2017). Antihypertensive effects of androgens in conscious, spontaneously hypertensive rats. The Journal of Steroid Biochemistry and Molecular Biology, 167, pp. 106-114. doi:10.1016/j.jsbmb.2016.11.016.
Perusquía M, et al. Antihypertensive Effects of Androgens in Conscious, Spontaneously Hypertensive Rats. J Steroid Biochem Mol Biol. 2017;167:106-114. PubMed PMID: 27888135.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antihypertensive effects of androgens in conscious, spontaneously hypertensive rats. AU - Perusquía,Mercedes, AU - Herrera,Nieves, AU - Ferrer,Mercedes, AU - Stallone,John N, Y1 - 2016/11/23/ PY - 2016/08/04/received PY - 2016/11/17/revised PY - 2016/11/20/accepted PY - 2016/11/27/pubmed PY - 2017/7/5/medline PY - 2016/11/27/entrez KW - 5α-Dihydrotestosterone KW - 5β-Dihydrotestosteronea KW - Androgens KW - Antihypertensive response KW - Blood pressure regulation KW - Hypertension KW - Hypotension KW - Testosterone SP - 106 EP - 114 JF - The Journal of steroid biochemistry and molecular biology JO - J. Steroid Biochem. Mol. Biol. VL - 167 N2 - Androgens are vasoactive steroids that induce acute vasodilation in a number of isolated vascular beds from different species, but the effects of these hormones on systemic blood pressure (BP) have been studied little. Although it has been reported that androgens exert systemic hypotensive effects through peripheral vasodilation in normotensive rats, there have not been any reports of systemic hypotensive effects of androgens in animals with hypertension. This study was designed to evaluate the acute effects of testosterone (TES) and its 5-reduced metabolites on systemic BP in hypertensive rats and to test the hypothesis that hypotestosteronemia may be involved in the pathogenesis of hypertension. Chronic, indwelling catheters were implanted in carotid artery and jugular vein of 18-21-week-old male spontaneously hypertensive rats (SHR) and normotensive-control Wistar-Kyoto (WKY) rats, for BP recording and drug administration, respectively. Bolus injections of TES, 5α- or 5β-dihydrotestosterone (5α- and 5β-DHT), were administrated cumulatively to conscious rats at doses of 0.1-100μmolkg-1min-1. 5β-DHT was also administrated during the pressor effect of Bay K 8644, an L-type voltage-operated Ca2+ channel (L-VOCC) agonist. In separate experiments, BP of orchidectomized normotensive male WKY and Wistar rats, with or without androgen-replacement therapy, was evaluated weekly for 10 weeks by tail-cuff plethysmography. TES and its metabolites reduced BP in a dose-dependent manner, while heart rate was reduced with some androgens at the highest doses. The hypotensive effects of androgens were markedly greater in SHR, with a rank order potency of: 5β-DHT>TES>5α-DHT. 5β-DHT, the most potent antihypertensive androgen, abolished the pressor response to Bay K 8644 in SHR. TES deprivation by orchidectomy increased BP in normotensive WKY and Wistar rats, but this hypertension was prevented by TES replacement therapy. BP responses to androgens are androgen structure-dependent. These data indicate that: 1) androgens play a significant role in the control of BP and may contribute to the pathogenesis of hypertension; 2) blockade of L-VOCC is involved in the antihypertensive effects of androgens, which are non-genomically mediated; and 3) hypotestosteronemia may be a risk factor for hypertension. SN - 1879-1220 UR - https://www.unboundmedicine.com/medline/citation/27888135/Antihypertensive_effects_of_androgens_in_conscious_spontaneously_hypertensive_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-0760(16)30330-2 DB - PRIME DP - Unbound Medicine ER -