Journal of cardiovascular pharmacology
-
J. Cardiovasc. Pharmacol. · Nov 2006
The effect of flutamide on systemic and renal hemodynamics in Zucker diabetic rats: paradoxic renal vasodilator response to endothelin-1 and TXA2 receptor activation in female sex.
There is increasing evidence that endogenous sex hormones regulate vascular reactivity, and testosterone may contribute to the worse prognosis for renal disease in men. Male Zucker diabetic rats exhibit improved renal hemodynamic responses after castration. It is, however, unclear whether endogenous testosterone affects renal and systemic microcirculatory responses in the female sex, especially in type 2 diabetes. ⋯ Flutamide administration to FZDR resulted in the reversal of abnormal systemic and renal alpha-1-mediated vasoconstriction and enhanced nitric oxide-mediated vasodilation. Flutamide caused a paradoxic but specific increase in renal perfusion during ET-1 and TXA2 receptor activation, which could be renoprotective in females. The salutary effects of flutamide on vascular reactivity in the FZDR may be mediated by a protein kinase C-dependent mechanism. These results are compatible with the notion that endogenous testosterone may regulate systemic and renal microcirculation in the female sex and in the type 2 diabetic state.