title: Mechanisms of vasorelaxation to testosterone in the rat aorta.
abstract: We have investigated the role of endothelium-derived relaxing factors, K(+) channels and steroid receptors in vasorelaxation to testosterone in the rat aorta. Testosterone (1 nM-mM) caused acute concentration-dependent vasorelaxation. Both indomethacin (10 microM) and flurbiprofen (10 microM) uncovered relaxant responses to testosterone. The action of indomethacin was inhibited by endothelial removal. N(G)-nitro-L-arginine methyl ester (L-NAME, 300 microM) had no effects on testosterone-induced responses. In the presence of indomethacin, the vasorelaxant potency of testosterone was reduced by depolarization with 60 mM KCl or charybdotoxin (100 nM), but not by glibenclamide (10 microM), 4-aminopyridine (1 mM) or barium chloride (30 microM). The responses to testosterone were not inhibited by flutamide (10 microM) or mifepristone (30 microM). Pre-treatment of the aorta with testosterone (100 microM) inhibited CaCl(2)-induced contraction. In the present study, we have demonstrated that testosterone causes acute vasorelaxations, which are modulated via endothelium-derived prostanoids. The responses uncovered by cyclooxygenase inhibitors are due to the activation of K(Ca) channels, while at higher concentrations, testosterone inhibits Ca(2+) influx.
authors.affiliation: Queen's Medical Centre, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, UK.
authors.forename: Patcharin
authors.initials: P
authors.lastname: Tep-areenan
authors.forename: David A
authors.initials: DA
authors.lastname: Kendall
authors.forename: Michael D
authors.initials: MD
authors.lastname: Randall
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005480:Flurbiprofen / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000726:Androgen Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D018999:Charybdotoxin; D013739:Testosterone; D005480:Flurbiprofen; D011189:Potassium Chloride; D005485:Flutamide; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin