Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway

Relaxation of the smooth muscle cells in the cavernosal arterioles and sinu ses results in increased blood flow into the penis, raising corpus cavernos um pressure to culminate in penile erection(1). Nitric oxide, released from non-adrenergic/non-cholinergic nerves, is considered the principle stimula tor of cavernosal smooth muscle relaxation(2-4), however, the inhibition of vasoconstrictors (that is, norepinephrine and endothelin-1, refs. 5-9) can not be ignored as a potential regulator of penile erection. The calcium-sen sitizing rho -A/Rho-kinase pathway may play a synergistic role in cavernosa l vasoconstriction to maintain penile flaccidity. Rho-kinase is known to in hibit myosin light chain phosphatase(10-12), and to directly phosphorylate myosin light-chain (in solution), altogether resulting in a net increase in activated myosin and the promotion of cellular contraction(10,11,13-16) Al though Rho-kinase protein and mRNA have been detected in cavernosal tissue( 17), the role of Rho-kinase in the regulation of cavernosal tone is unknown . Using pharmacologic antagonism (Y-27632, ref. 13, 18), we examined the ro le of Rho-kinase in cavernosal tone, based on the hypothesis that antagonis m of Rho-kinase results in increased corpus cavernosum pressure, initiating the erectile response independently of nitric oxide. Our finding, that Rho -kinase antagonism stimulates rat penile erection independently of nitric o xide, introduces a potential alternate avenue for the treatment of erectile dysfunction.