Involvement of Rho-Kinase Signaling Pathways in Nerve Evoked and Spontaneous Contractions of the Guinea Pig Prostate

Abstract

Men with benign prostatic hyperplasia commonly experience irritative lower urinary tract symptoms, which are due at least in part to enhanced prostatic smooth muscle tone. To provide some insight into the changes that occur in prostatic contractility with age, we examined the contribution of rho-kinase dependent Ca(2+) sensitization in neurogenic and spontaneous contractions of young and aging guinea pig prostates. We used conventional tension recording and electrophysiological intracellular microelectrode recording techniques. The Rho-kinase inhibitor Y-27632 (10 and 100 μM) significantly inhibited electrical field stimulated evoked (neurogenic) contractions in the guinea pig prostate in a dose dependent manner. In addition, Y-27632 (1 and 10 μM) similarly suppressed tetrodotoxin insensitive spontaneous contractions in dose dependent fashion. While Y-27632 at 10 μM decreased spontaneous contractions of young and aging guinea pig prostates, as evidenced by a significant decrease in the AUC, there was no significant difference in the degree of inhibition between the 2 age groups. In contrast to contractile activity, Y-27632 did not affect the generation or modulation of spontaneous slow wave electrical activity, which underlies spontaneous contractions. There are strong indicators that Rho-kinase signaling pathways have a significant role in prostatic smooth muscle contractility, most likely independent of cytosolic Ca(2+) levels. Features of the rho-kinase pathway may well represent alternative, novel future therapeutic targets to reduce prostatic contractility, thereby alleviating the lower urinary tract symptoms arising from benign prostatic hyperplasia.