Lucía Isidoro1,2, Mercedes Ferrer1, Mercedes Perusquía2. 1. a Departamento de Fisiología, Facultad de Medicina , Universidad Autónoma de Madrid , Madrid , Spain. 2. b Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología , Universidad Nacional Autónoma de México , Mexico City , Mexico.
Abstract
BACKGROUND: Testosterone, 5α- and 5β-dihydrotestosterone (-DHT) induce an acute in vitro vasorelaxation and in vivo vasodepressor, hypotensive and antihypertensive responses. Our aim was to study whether androgen-induced blood pressure (BP) reduction is involved with a blockade of Ca2+ influx through L-type voltage-operated calcium channels (L-VOCCs) and/or the signaling pathways of α1-adrenoceptors to induce vasoconstriction, which are one of the major mechanisms of BP maintenance. MATERIALS AND METHODS: The relaxing potency and efficacy of each androgen in large conduit (thoracic aorta) and resistance (mesenteric) arteries from male hypertensive (SHR) and normotensive (WKY) rats were established. Blood vessels were isometrically recorded and precontracted with KCl or phenylephrine (Phe). RESULTS: Androgens induced concentration-dependent vasorelaxation in precontracted arteries from SHR and WKY rats. 5β-DHT was always the most potent vasorelaxant in arteries from SHR. The KCl-induced contraction resulted significantly more sensitive to androgen-induced vasorelaxation than the Phe-induced contraction. On Phe-induced contraction, 5β-DHT was more potent in the mesenteric artery than in the thoracic aorta. CONCLUSIONS: The vasorelaxation induced by androgens is mainly mediated by blocking L-VOCCs and in lesser extent by the blockade of multiple signaling pathways operative during α-adrenoceptor-induced vasoconstriction. 5β-DHT regulates vascular resistance and BP by mainly acting in the mesenteric arterial bed, which may explain its outstanding antihypertensive response previously reported.
BACKGROUND:Testosterone, 5α- and 5β-dihydrotestosterone (-DHT) induce an acute in vitro vasorelaxation and in vivo vasodepressor, hypotensive and antihypertensive responses. Our aim was to study whether androgen-induced blood pressure (BP) reduction is involved with a blockade of Ca2+ influx through L-type voltage-operated calcium channels (L-VOCCs) and/or the signaling pathways of α1-adrenoceptors to induce vasoconstriction, which are one of the major mechanisms of BP maintenance. MATERIALS AND METHODS: The relaxing potency and efficacy of each androgen in large conduit (thoracic aorta) and resistance (mesenteric) arteries from male hypertensive (SHR) and normotensive (WKY) rats were established. Blood vessels were isometrically recorded and precontracted with KCl or phenylephrine (Phe). RESULTS: Androgens induced concentration-dependent vasorelaxation in precontracted arteries from SHR and WKY rats. 5β-DHT was always the most potent vasorelaxant in arteries from SHR. The KCl-induced contraction resulted significantly more sensitive to androgen-induced vasorelaxation than the Phe-induced contraction. On Phe-induced contraction, 5β-DHT was more potent in the mesenteric artery than in the thoracic aorta. CONCLUSIONS: The vasorelaxation induced by androgens is mainly mediated by blocking L-VOCCs and in lesser extent by the blockade of multiple signaling pathways operative during α-adrenoceptor-induced vasoconstriction. 5β-DHT regulates vascular resistance and BP by mainly acting in the mesenteric arterial bed, which may explain its outstanding antihypertensive response previously reported.
Authors: Thomas Van den Broeck; Mohammad Ayodhia Soebadi; Annelies Falter; Lore Raets; Jolien Duponselle; Joline Lootsma; Alexander Heintz; Uchelly Philtjens; Lien Hofkens; Arantxa Gonzalez-Viedma; Karel Driesen; Peter Sandner; Maarten Albersen; Bert Brône; Koenraad Van Renterghem Journal: Sex Med Date: 2019-11-22 Impact factor: 2.491
Authors: Diva M Villalpando; Carlos M Verdasco-Martín; Ignacio Plaza; Juan Gómez-Rivas; Fermín R de Bethencourt; Morris Villarroel; José L García; Cristina Otero; Mercedes Ferrer Journal: Int J Vasc Med Date: 2020-12-08