title: Pharmacological evidence that Ca²+ channels and, to a lesser extent, K+ channels mediate the relaxation of testosterone in the canine basilar artery.
abstract: Testosterone induces vasorelaxation through non-genomic mechanisms in several isolated blood vessels, but no study has reported its effects on the canine basilar artery, an important artery implicated in cerebral vasospasm. Hence, this study has investigated the mechanisms involved in testosterone-induced relaxation of the canine basilar artery. For this purpose, the vasorelaxant effects of testosterone were evaluated in KCl- and/or PGF(₂α)-precontracted arterial rings in vitro in the absence or presence of several antagonists/inhibitors/blockers; the effect of testosterone on the contractile responses to CaCl₂ was also determined. Testosterone (10-180 μM) produced concentration-dependent relaxations of KCl- or PGF(₂α)-precontracted arterial rings which were: (i) unaffected by flutamide (10 μM), DL-aminoglutethimide (10 μM), actinomycin D (10 μM), cycloheximide (10 μM), SQ 22,536 (100 μM) or ODQ (30 μM); and (ii) significantly attenuated by the blockers 4-aminopyridine (K(V); 1 mM), BaCl₂ (K(IR); 30 μM), iberiotoxin (BK(Ca²+); 20 nM), but not by glybenclamide (K(ATP); 10 μM). In addition, testosterone (31, 56 and 180 μM) and nifedipine (0.01-1 μM) produced a concentration-dependent blockade of the contraction to CaCl₂ (10 μM to 10 mM) in arterial rings depolarized by 60mM KCl. These results, taken together, show that testosterone relaxes the canine basilar artery mainly by blockade of voltage-dependent Ca²+ channels and, to a lesser extent, by activation of K+ channels (K(IR), K(V) and BK(Ca²+)). This effect does not involve genomic mechanisms, production of cAMP/cGMP or the conversion of testosterone to 17β-estradiol.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330, México D.F., Mexico.
authors.forename: Martha B
authors.initials: MB
authors.lastname: Ramírez-Rosas
authors.forename: Luis E
authors.initials: LE
authors.lastname: Cobos-Puc
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Muñoz-Islas
authors.forename: Abimael
authors.initials: A
authors.lastname: González-Hernández
authors.forename: Araceli
authors.initials: A
authors.lastname: Sánchez-López
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
authors.forename: Antoinette
authors.initials: A
authors.lastname: Maassenvandenbrink
authors.forename: David
authors.initials: D
authors.lastname: Centurión
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000616:Aminoglutethimide / Q000494:pharmacology; D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D059002:Androgen Receptor Antagonists; D047072:Aromatase Inhibitors; D017609:Barium Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002712:Chlorides; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011500:Protein Synthesis Inhibitors; D011810:Quinoxalines; D014665:Vasodilator Agents; D000616:Aminoglutethimide; C024986:barium chloride; C017759:9-(tetrahydro-2-furyl)-adenine; D003609:Dactinomycin; D013739:Testosterone; D005485:Flutamide; D003513:Cycloheximide; D015761:4-Aminopyridine; D009543:Nifedipine; D000225:Adenine