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Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation

Authors :
Kanchan Chitaley
Ronald W. Lewis
Christopher J. Wingard
R. Clinton Webb
Thomas M. Mills
Source :
Journal of Applied Physiology. 91:1269-1273
Publication Year :
2001
Publisher :
American Physiological Society, 2001.

Abstract

A recent report from this laboratory (Chitaley K, Wingard C, Webb R, Branam H, Stopper V, Lewis R, and Mills T. Nature Medicine 7: 119–122, 2001) showed that inhibition of Rho-kinase increased the erectile response (intracavernosal pressure and mean arterial pressure) by a process that does not require nitric oxide or cGMP. The present study investigated whether vasoconstrictor agents, which are active in the penis, act via the Rho-kinase pathway. Western analysis revealed RhoA and Rho-kinase protein in the penis. Treatment with the selective Rho-kinase inhibitor Y-27632 significantly increased the magnitude of the erectile response. Intracavernous administration of endothelin-1 (ET-1; 50 pmol) or methoxamine (10 μg/kg) reduced the erectile response to autonomic stimulation. If Y-27632 was given before ET-1 or methoxamine, the vasoconstrictor effect was reduced, and intracavernosal pressure and mean arterial pressure remained elevated. However, when given after methoxamine, Y-27632 had a reduced vasodilatory effect, and Y-27632 had no vasodilatory effect when given after ET-1. These findings suggest that ET-1 and methoxamine increase Rho-kinase activity in the cavernous circulation and support the hypothesis that the vasoconstriction that maintains the penis in the nonerect state is mediated, in part, by the Rho-kinase pathway.

Details

ISSN :
15221601 and 87507587
Volume :
91
Database :
OpenAIRE
Journal :
Journal of Applied Physiology
Accession number :
edsair.doi.dedup.....c105f5fc3660c185fe1f0f0d66f9579c