Role of rho-kinase activity in angiotensin II-induced contraction of rabbit clitoral cavernosum smooth muscle.
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-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML7) were used in rabbit clitoral cavernosum smooth muscle (CSM). N(G)-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 II, dose-dependently. However, ML7 did not affect the contractile response to ANG II except in the high concentrations of ML7. Y-27632 inhibited contraction with phenylephrine (PhE), but 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 Ca(2+) sensitivity mediated through the RhoA/Rho-kinase signal pathway is involved in the control by ANG II of the clitoral CSM tone. RhoA/Rho-kinase pathway acts in the ANG II-induced contraction independently of the NO pathway.
Park
J K
JK
Department of Urology, Chonbuk National University Medical School, Chonju, South Korea. rain@moak.chonbuk.ac.kr
Lee
S O
SO
Kim
Y G
YG
Kim
S H
SH
Koh
G Y
GY
Cho
K W
KW
D000577:Amides / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002987:Clitoris / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D007537:Isometric Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009219:Myosin-Light-Chain Kinase; D009281:Naphthalenes / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D015398:Signal Transduction; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000577:Amides; D001381:Azepines; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009281:Naphthalenes; D011725:Pyridines; C070571:ML 7; D000804:Angiotensin II; C108830:Y 27632; D010656:Phenylephrine; D009569:Nitric Oxide; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D020742:rhoA GTP-Binding Protein