title: Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits.
abstract: Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone (10(-8) to 10(-4)M) induced relaxation of precontracted arteries, without significant differences between control and diabetic rabbits. Both in control and diabetic rabbits endothelium removal inhibited testosterone relaxant action. In arteries with endothelium, incubation with indomethacin (10(-5)M), N(G)-nitro-l-arginine (10(-5)M) or tetraethylammonium (10(-5)M) did not modify relaxations to testosterone neither in control nor in diabetic rabbits. In endothelium-denuded arteries indomethacin enhanced the relaxant action of testosterone, both in control and diabetic rabbits. In arteries from diabetic rabbits, eNOS, iNOS and COX-1 expression and testosterone-induced release of thromboxane A(2) and prostacyclin were not significantly different from those observed in control rabbits. However, COX-2 expression was significantly lower in diabetic rabbits that in control rabbits. In nominally Ca(2+)-free medium, cumulative addition of CaCl2 (10(-5) to 3x10(-2)M) contracted previously depolarized arteries. Testosterone (10(-4)M) inhibited CaCl2 contractions of the renal artery both in control and diabetic rabbits. These results show that testosterone relaxes the renal artery both in control and diabetic rabbits. This relaxation is modulated by muscular thromboxane A(2), it is partially mediated by endothelial prostacyclin, and it involves the blocking of extracellular Ca2+ entry. Diabetes does not modify the mechanisms involved in the relaxant action of testosterone in the rabbit renal artery.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Valencia, Avda. Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Vannina G
authors.initials: VG
authors.lastname: Marrachelli
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Miranda
authors.forename: José M
authors.initials: JM
authors.lastname: Centeno
authors.forename: María C
authors.initials: MC
authors.lastname: Burguete
authors.forename: María
authors.initials: M
authors.lastname: Castelló-Ruiz
authors.forename: Teresa
authors.initials: T
authors.lastname: Jover-Mengual
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Pérez
authors.forename: Juan B
authors.initials: JB
authors.lastname: Salom
authors.forename: Germán
authors.initials: G
authors.lastname: Torregrosa
authors.forename: Enrique
authors.initials: E
authors.lastname: Alborch
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D044062:Prostaglandins I / Q000378:metabolism; D011817:Rabbits; D012077:Renal Artery / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction; D013739:Testosterone / Q000097:blood / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism; D014664:Vasodilation
chemical_list: D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D026902:Potassium Channel Blockers; D044062:Prostaglandins I; D019335:Nitroarginine; D013739:Testosterone; D013928:Thromboxane A2; D019789:Tetraethylammonium; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011188:Potassium; D002118:Calcium; D007213:Indomethacin