Physiological antagonism between endothelial NO and the Rho/Rho-kinase signaling pathway regulates erectile function where the Rho/Rho-kinase pathway maintains penile flaccidity and antagonism of this pathway leads to corpus cavernosum relaxation and penile erection. In this issue, Priviero et al. investigated the hypothesis that the basal release of NO from endothelial cells modulates contractile activity in the corpus cavernosum via inhibition of Rho/Rho-kinase signaling. By using endothelial nitric-oxide synthase (−/−) [eNOS(−/−)] mice, the authors demonstrate decreased responsiveness to Rho-kinase inhibitors H-1152 [(S)-(+)-2-methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl]homopiperazine] and Y-27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide] associated with increased expression of Rho-associated proteins and kinases in the corpus cavernosum, suggesting that the attenuated response to Rho-kinase inhibition in contractile responses in eNOS(−/−) mice is a result of increased Rho signaling. These novel results provide new insight into the regulation of erectile function through the Rho-kinase signaling pathway.
See article at J Pharmacol Exp Ther 2010, 333:184–192.
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