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

被引:70
作者
Mills, TM [1 ]
Chitaley, K
Wingard, CJ
Lewis, RW
Webb, RC
机构
[1] Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA
[2] Med Coll Georgia, Dept Surg, Urol Sect, Augusta, GA 30912 USA
关键词
penile erection; vasodilation; penis; methoxamine; endothelin-1;
D O I
10.1152/jappl.2001.91.3.1269
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 mug/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.
引用
收藏
页码:1269 / 1273
页数:5
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