Role of Rho-Kinase Activity in Angiotensin II-Induced Contraction of Corpus Cavernosum Smooth Muscle in the Rabbit.
- Author:
Myung Ki KIM
1
;
Jong Kwan PARK
Author Information
1. Department of Urology, Chonbuk National University Medical School, Jeonju, Korea. rain@moak.chonbuk.ac.kr
- Publication Type:Original Article
- Keywords:
Angiotensin II;
Ca2 sensitization;
Corpus cavernosum smooth muscle;
Myosin light chain kinase;
RhoA/Rho-kinase
- MeSH:
Angiotensin II;
Angiotensins*;
Calcium;
Muscle, Smooth*;
Myofibrils;
Myosin-Light-Chain Kinase;
Nitric Oxide Synthase;
Phenylephrine;
Relaxation;
rho-Associated Kinases*
- From:Korean Journal of Andrology
2003;21(1):32-37
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: RhoA/Rho-kinase regulates vascular tone via a calcium sensitization mechanism. Stimulation of the AT1 receptor by angiotensin (ANG) II activates the Rho A/Rho-kinase signaling pathway. However, its role in corpus cavernosum smooth muscle (PCSM) has not been known. MATERIALS AND METHODS: Isometric tension measurements were performed in rabbit PCSM using a selective Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide (Y-27632), and a selective myosin light chain kinase (MLCK) inhibitor, 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML7). RESULTS: Y-27632 significantly attenuated contractions induced by ANG II in a dose-dependent fashion. However, ML7 did not affect the contractile response to ANG II except at high concentration. Y-27632 inhibited contraction in response to phenylephrine (PhE), but ML7 did not. A nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester, did not affect Y-27632-induced relaxation of the strip contracted with PhE. CONCLUSIONS: A G-protein-coupled increase in myofilament Ca2+ sensitivity, mediated through the RhoA/Rho-kinase signaling pathway, is involved in the regulation of the PCSM tone induced by ANG II. The RhoA/Rho-kinase pathway acts in AGN II-induced contraction independent of the NO pathway.