Testosterone dependence of salt-induced hypertension in Sabra rats and role of renal alpha(2)-adrenoceptor subtypes.

Abstract

This study investigated the importance of the male sex hormone testosterone on salt-induced hypertension, renal alpha(2)-adrenoceptor subtype distribution, and gene expression in salt-sensitive (SBH) male Sabra rats. Comparisons of blood pressure and renal alpha(2)-adrenoceptor subtype gene expression and receptor densities have been made among sham-operated rats, and gonadectomized rats treated or not with testosterone and submitted to normal or high salt diet for 6 weeks. In intact rats, only alpha(2B)-adrenoceptors were detected in this rat strain independent of the diet. In these rats, high salt diet increases blood pressure and up-regulates gene expression and density of alpha(2)-adrenoceptors. Gonadectomy abolishes the hypertensive response to salt overload, decreases gene expression and density of alpha(2B)-adrenoceptors, and prevents their salt-induced up-regulation. After gonadectomy, increased gene expression and a detectable density of alpha(2A)-adrenoceptors are observed at similar levels in normal and high salt diet. In gonadectomized rats, testosterone replacement restores salt-induced hypertension, density of renal alpha(2B)-adrenoceptors, and gene expression to the intact levels observed both under normal and high salt diet. Furthermore, the alpha(2A)-adrenoceptor subtype is not detected in these conditions. If the increase in renal alpha(2B)-adrenoceptor subtypes is indicative of the hypertensive phenotype, the presence of the alpha(2A)-adrenoceptor appears associated with a state of salt resistance in male SBH rats. In conclusion, testosterone is needed for the full expression of salt-induced hypertension in male salt-sensitive Sabra rats. Renal densities of alpha(2)-adrenoceptor subtypes are under control of the testicles and are differentially regulated by testosterone.