Rho Kinase Contributes to Androgen Amplification of Renal Vasoconstrictor Responses in the Spontaneously Hypertensive Rat

Abstract

Androgens modulate vascular tone and hypertension development. Rho kinase contributes to norepinephrine- (NE) and vasopressin- (AVP) induced vasoconstriction. This study tested the hypothesis that Rho kinase contributes to androgen amplification of renal vasoconstrictor responses to NE or AVP in isolated perfused kidney of spontaneously hypertensive rats (SHRs).SHRs (5 weeks) underwent sham operation, castration, or castration with testosterone replacement. At 16-17 weeks, mean arterial pressure and heart rate were measured in conscious SHRs. Renal vascular reactivity to NE (10 to 10 mol) and to AVP (10 to 10 mol) was assessed in an isolated perfused kidney preparation before and after Rho kinase inhibitor treatment (fasudil; 15 microM). Castration reduced mean arterial pressure, whereas testosterone treatment of castrated SHRs increased mean arterial pressure significantly. The dose-response curves to NE and AVP obtained in isolated perfused kidneys from castrated SHRs were displaced to the right of those obtained in sham-operated and castrated + testosterone-treated SHRs. Fasudil treatment produced a rightward shift in the dose-response curves for each agonist in all of the groups and greatly attenuated the differences in renal vascular reactivity to NE and AVP among the 3 groups of SHRs.Collectively, these findings indicate that androgen modulation of hypertension development in the SHR involves a fasudil-sensitive pathway and suggest that further study is warranted in this area.