Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits

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 A₂ 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 Ca²⁺-free medium, cumulative addition of CaCl₂ (10^?5 to 3 × 10^?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 A₂, 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.