title: Antihypertensive effects of androgens in conscious, spontaneously hypertensive rats.
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.affiliation: Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, México City 04510, Mexico. Electronic address: perusqui@unam.mx.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Perusquía
authors.affiliation: Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, México City 04510, Mexico.
authors.forename: Nieves
authors.initials: N
authors.lastname: Herrera
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain; Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ferrer
authors.affiliation: 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.
authors.forename: John N
authors.initials: JN
authors.lastname: Stallone
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003243:Consciousness / Q000187:drug effects*; D013196:Dihydrotestosterone / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012307:Risk Factors; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000728:Androgens; D000959:Antihypertensive Agents; D020746:Calcium Channels, L-Type; D013196:Dihydrotestosterone; D013739:Testosterone
keywords: 5α-Dihydrotestosterone; 5β-Dihydrotestosteronea; Androgens; Antihypertensive response; Blood pressure regulation; Hypertension; Hypotension; Testosterone