This Article Full Text Full Text (PDF) All Versions of this Article: 149/5/2517    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Montaño, L. M. Articles by Perusquía, M. PubMed PubMed Citation Articles by Montaño, L. M. Articles by Perusquía, M.

Relaxation of Androgens on Rat Thoracic Aorta: Testosterone Concentration Dependent Agonist/Antagonist L-Type Ca²⁺ Channel Activity, and 5β-Dihydrotestosterone Restricted to L-Type Ca²⁺ Channel Blockade

Universidad Nacional Autónoma de México (M.P.), Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, and Facultad de Medicina (L.M.M., A.F., E.F.-S.), Departamento de Farmacología, México D.F. 04510; Departamento de Hiperreactividad Bronquial (V.C.), Instituto Nacional de Enfermedades Respiratorias, México D.F. 14080; and Departamento de Neurobiología (E.C.), División de Investigación en Neurociencias, Instituto Nacional de Psiquiatria Ramón de la Fuente Muñíz, México D.F. 14370

Address all correspondence and requests for reprints to: Dr. Mercedes Perusquía, Apartado Postal 70228, México D.F. 04510. E-mail: perusqui{at}servidor.unam.mx.

Androgen vasorelaxing action is a subject of recent interest. We investigated the involvement of L-type voltage-operated Ca²⁺ channels (L-VOCCs), K⁺ channels, intracellular Ca²⁺ concentration ([Ca²⁺]i), and cAMP in the vasorelaxing effect of testosterone and 5β-dihydrotestosterone (5β-DHT) on rat thoracic aorta. Isolated aortic rings were used to study the vasorelaxing potency of testosterone and 5β-DHT on KCl- and noradrenaline-induced contractions. Patch-clamp was used to analyze androgen effects on Ca²⁺ inward and K⁺ outward currents. The fluorescence technique was used to evaluate [Ca²⁺]i in single myocytes; moreover, simultaneous measurements of [Ca²⁺]i and vascular contraction were evaluated. 5β-DHT was more potent than testosterone to relax KCl-induced contraction, but they were equipotent to relax noradrenaline contraction. L-type Ca²⁺ currents were blocked by nifedipine, both androgens, and an estrogen in a concentration-dependent manner, and the order of potency was: testosterone > nifedipine > 5β-DHT > 17β-estradiol. We observed that testosterone has different mechanism of action by the concentration range used: at nM concentrations it was a powerful L-VOCCs antagonist, whereas at µM concentrations it was observed that: 1) its Ca²⁺ antagonist property is reverted by increasing the L-type inward Ca²⁺ currents (Ca²⁺ agonist property); and 2) the [Ca²⁺]i and cAMP production was increased. The total K⁺ currents were unaffected by testosterone or 5β-DHT. The data show that 5β-DHT-induced vasorelaxation is due to its selective blockade on L-VOCCs (from nM to µM concentrations), but testosterone-induced vasorelaxation involves concentration-dependent additional mechanisms: acting as an L-VOCCs antagonist at low concentrations, and increasing [Ca²⁺]i and cAMP production at high concentrations.