Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation.
Mills, Thomas M., Kanchan Chitaley, Christopher J. Wingard, Ronald W. Lewis, and R.
Clinton Webb.
Department of Physiology and Urology Section, Department of Surgery, Medical
College of Georgia, Augusta, Georgia 30912«hyphen»3000
APStracts 8:0324A, 2001.
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.«fnc1»1
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.
Received 26 March 2001; accepted in final form 6 June 2001
APS Manuscript Number A287-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 June 2001