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Relaxation of androgens on rat thoracic aorta: testosterone concentration dependent agonist/antagonist L-type Ca2+ channel activity, and 5beta-dihydrotestosterone restricted to L-type Ca2+ channel blockade.
Endocrinology 2008; 149(5):2517-26E

Abstract

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

Authors+Show Affiliations

Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, and Facultad de Medicina, Departamento de Farmacología, México D.F. 04510.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18276759

Citation

Montaño, Luis M., et al. "Relaxation of Androgens On Rat Thoracic Aorta: Testosterone Concentration Dependent Agonist/antagonist L-type Ca2+ Channel Activity, and 5beta-dihydrotestosterone Restricted to L-type Ca2+ Channel Blockade." Endocrinology, vol. 149, no. 5, 2008, pp. 2517-26.
Montaño LM, Calixto E, Figueroa A, et al. Relaxation of androgens on rat thoracic aorta: testosterone concentration dependent agonist/antagonist L-type Ca2+ channel activity, and 5beta-dihydrotestosterone restricted to L-type Ca2+ channel blockade. Endocrinology. 2008;149(5):2517-26.
Montaño, L. M., Calixto, E., Figueroa, A., Flores-Soto, E., Carbajal, V., & Perusquía, M. (2008). Relaxation of androgens on rat thoracic aorta: testosterone concentration dependent agonist/antagonist L-type Ca2+ channel activity, and 5beta-dihydrotestosterone restricted to L-type Ca2+ channel blockade. Endocrinology, 149(5), pp. 2517-26. doi:10.1210/en.2007-1288.
Montaño LM, et al. Relaxation of Androgens On Rat Thoracic Aorta: Testosterone Concentration Dependent Agonist/antagonist L-type Ca2+ Channel Activity, and 5beta-dihydrotestosterone Restricted to L-type Ca2+ Channel Blockade. Endocrinology. 2008;149(5):2517-26. PubMed PMID: 18276759.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relaxation of androgens on rat thoracic aorta: testosterone concentration dependent agonist/antagonist L-type Ca2+ channel activity, and 5beta-dihydrotestosterone restricted to L-type Ca2+ channel blockade. AU - Montaño,Luis M, AU - Calixto,Eduardo, AU - Figueroa,Alejandra, AU - Flores-Soto,Edgar, AU - Carbajal,Verónica, AU - Perusquía,Mercedes, Y1 - 2008/02/14/ PY - 2008/2/16/pubmed PY - 2008/6/11/medline PY - 2008/2/16/entrez SP - 2517 EP - 26 JF - Endocrinology JO - Endocrinology VL - 149 IS - 5 N2 - Androgen vasorelaxing action is a subject of recent interest. We investigated the involvement of l-type voltage-operated Ca(2+) channels (L-VOCCs), K(+) channels, intracellular Ca(2+) concentration ([Ca(2+)]i), and cAMP in the vasorelaxing effect of testosterone and 5beta-dihydrotestosterone (5beta-DHT) on rat thoracic aorta. Isolated aortic rings were used to study the vasorelaxing potency of testosterone and 5beta-DHT on KCl- and noradrenaline-induced contractions. Patch-clamp was used to analyze androgen effects on Ca(2+) inward and K(+) outward currents. The fluorescence technique was used to evaluate [Ca(2+)]i in single myocytes; moreover, simultaneous measurements of [Ca(2+)]i and vascular contraction were evaluated. 5beta-DHT was more potent than testosterone to relax KCl-induced contraction, but they were equipotent to relax noradrenaline contraction. l-type Ca(2+) currents were blocked by nifedipine, both androgens, and an estrogen in a concentration-dependent manner, and the order of potency was: testosterone > nifedipine > 5beta-DHT > 17beta-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 mum concentrations it was observed that: 1) its Ca(2+) antagonist property is reverted by increasing the l-type inward Ca(2+) currents (Ca(2+) agonist property); and 2) the [Ca(2+)]i and cAMP production was increased. The total K(+) currents were unaffected by testosterone or 5beta-DHT. The data show that 5beta-DHT-induced vasorelaxation is due to its selective blockade on L-VOCCs (from nm to microm concentrations), but testosterone-induced vasorelaxation involves concentration-dependent additional mechanisms: acting as an L-VOCCs antagonist at low concentrations, and increasing [Ca(2+)]i and cAMP production at high concentrations. SN - 0013-7227 UR - https://www.unboundmedicine.com/medline/citation/18276759/Relaxation_of_androgens_on_rat_thoracic_aorta:_testosterone_concentration_dependent_agonist/antagonist_L_type_Ca2+_channel_activity_and_5beta_dihydrotestosterone_restricted_to_L_type_Ca2+_channel_blockade_ L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2007-1288 DB - PRIME DP - Unbound Medicine ER -