Role of rho-kinase activity in angiotensin II-induced contraction of rabbit clitoral cavernosum smooth muscle

Abstract

Isometric tension measurement using a selective Rho-kinase inhibitor (+)- (R)-trans4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632) and a selective myosin light chain kinase (MLCK) inhibitor 1-(5-iodonaphthalene-i-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML7) were used in rabbit clitoral cavernosum smooth muscle (CSM). NI-nitro-L-arginine methyl ester (L-NAME) was used to evaluate the relationship between NO release and Rho-kinase. Y-27632 significantly attenuated contractions induced by ANG 11, dose-dependently. However, ML7 did not affect the contractile response to ANG 11 except in the high concentrations of ML7. Y-27632 inhibited contraction with phenylephrine (PhE), hut ML7 did not inhibit contraction with PhE. Nitric oxide synthase inhibitor (NAME) did not affect the Y-27632-induced relaxation in the pre-contracted strip with PhE. The present study demonstrates that G-protein-coupled increase in myofilament Ca2+ sensitivity mediated through the RhoA/Rho-kinase signal pathway is involved in the control by ANG 11 of the clitoral CSM tone. RhoA/Rho-kinase pathway acts in the ANG II-induced contraction independently of the NO pathway.