Mercedes Perusquía1, Daniela Contreras2, Nieves Herrera2. 1. Departamento de Biología Celular y Fisiología, Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, 04510, Mexico City, Mexico. perusqui@unam.mx. 2. Departamento de Biología Celular y Fisiología, Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, 04510, Mexico City, Mexico.
Abstract
PURPOSE: Hypotestosteronemia is an aging-associated disease. Little is known about experimental evidence linking androgen deficiency to hypertension. Various androgens are acute vasodilators, both in vitro and in vivo. We aimed to systematically investigate blood pressure (BP) in male normotensive intact or orchidectomized (ORX) Wistar and Wistar-Kyoto rats. Furthermore, we studied the acute antihypertensive responses of testosterone (TES), its precursor (DHEA), or its 5β-reduced metabolite (5β-DHT) in conscious, unrestrained, hypertensive Wistar rats caused by orchidectomy to determine their potency and efficacy. Similarly, the mechanism of their action mediated by nitric oxide (NO) was studied in vivo. METHODS: BP of ORX rats was evaluated weekly for 18 weeks by tail cuff plethysmography. Subsequently, BP of ORX Wistar rats was measured by chronic indwelling vascular catheters, arterial, and venous catheters were implanted under anesthesia for BP recording and androgen administration, respectively. Then, a dose-response curve of each androgen was performed. Likewise, the dose-response curve of 5β-DHT, the most potent androgen, was repeated in the presence of a nonselective NO synthase inhibitor (L-NAME) or an inhibitor of endothelial NO synthesis (Endothelin-1). RESULTS: ORX rats progressively increased systolic/diastolic BP (167 ± 2.8/141 ± 3.3 mmHg) over 18 weeks. No difference was found between strains. The BP was reduced in a dose-dependent manner caused by i.v. bolus injection of each androgen, with a rank order of potency of: 5β-DHT = DHEA>>TES. Dose-dependent antihypertension induced by 5β-DHT in ORX rats was not abolished in the presence of L-NAME or Endothelin-1. CONCLUSIONS: These in vivo experimental findings reveal that hypotestosteronemia is a determining factor for the development of hypertension which is powerfully reduced by androgen administration, and 5β-DHT induces a potent and effective antihypertensive response by a NO-independent mechanism.
PURPOSE: Hypotestosteronemia is an aging-associated disease. Little is known about experimental evidence linking androgen deficiency to hypertension. Various androgens are acute vasodilators, both in vitro and in vivo. We aimed to systematically investigate blood pressure (BP) in male normotensive intact or orchidectomized (ORX) Wistar and Wistar-Kyoto rats. Furthermore, we studied the acute antihypertensive responses of testosterone (TES), its precursor (DHEA), or its 5β-reduced metabolite (5β-DHT) in conscious, unrestrained, hypertensiveWistar rats caused by orchidectomy to determine their potency and efficacy. Similarly, the mechanism of their action mediated by nitric oxide (NO) was studied in vivo. METHODS: BP of ORX rats was evaluated weekly for 18 weeks by tail cuff plethysmography. Subsequently, BP of ORX Wistar rats was measured by chronic indwelling vascular catheters, arterial, and venous catheters were implanted under anesthesia for BP recording and androgen administration, respectively. Then, a dose-response curve of each androgen was performed. Likewise, the dose-response curve of 5β-DHT, the most potent androgen, was repeated in the presence of a nonselective NO synthase inhibitor (L-NAME) or an inhibitor of endothelial NO synthesis (Endothelin-1). RESULTS: ORX rats progressively increased systolic/diastolic BP (167 ± 2.8/141 ± 3.3 mmHg) over 18 weeks. No difference was found between strains. The BP was reduced in a dose-dependent manner caused by i.v. bolus injection of each androgen, with a rank order of potency of: 5β-DHT = DHEA>>TES. Dose-dependent antihypertension induced by 5β-DHT in ORX rats was not abolished in the presence of L-NAME or Endothelin-1. CONCLUSIONS: These in vivo experimental findings reveal that hypotestosteronemia is a determining factor for the development of hypertension which is powerfully reduced by androgen administration, and 5β-DHT induces a potent and effective antihypertensive response by a NO-independent mechanism.
Entities:
Keywords:
5β-dihydrotestosterone; Androgen deficiency; Androgen-regulated blood pressure; Androgens; Antihypertensive response; Hypertension in aging men
Authors: Judith S Brand; Maroeska M Rovers; Bu B Yeap; Harald J Schneider; Tomi-Pekka Tuomainen; Robin Haring; Giovanni Corona; Altan Onat; Marcello Maggio; Claude Bouchard; Peter C Y Tong; Richard Y T Chen; Masahiro Akishita; Jourik A Gietema; Marie-Hélène Gannagé-Yared; Anna-Lena Undén; Aarno Hautanen; Nicolai P Goncharov; Philip Kumanov; S A Paul Chubb; Osvaldo P Almeida; Hans-Ulrich Wittchen; Jens Klotsche; Henri Wallaschofski; Henry Völzke; Jussi Kauhanen; Jukka T Salonen; Luigi Ferrucci; Yvonne T van der Schouw Journal: PLoS One Date: 2014-07-14 Impact factor: 3.240