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KMID : 0356420030210010032
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Journal of Korean Andrology
2003 Volume.21 No. 1 p.32 ~ p.37
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Role of Rho-Kinase Activity in Angiotensin II-Induced Contraction of Corpus Cavernosum Smooth Muscle in the Rabbit
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Kim Myung-Ki
Park Jong-Kwan
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Abstract
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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.
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KEYWORD
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Angiotensin Ⅱ, CA(2+) sensitization, Corpus cavernosum smooth muscle, Myosin light chain kinase, RhoA/Rho-kinase
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