The promise of inhibition of smooth muscle tone as a treatment for erectile dysfunction: where are we now?

Abstract

Ten years ago, the inhibition of Rho kinase by intracavernosal injection of Y-27632 was found to induce an erectile response. This effect did not require activation of nitric oxide-mediated signaling, introducing a novel target pathway for the treatment of erectile dysfunction (ED), with potential added benefit in cases where nitric oxide bioavailability is attenuated (and thus phosphodiesterase type 5 (PDE5) inhibitors are less efficacious). Rho-kinase antagonists are currently being developed and tested for a wide range of potential uses. The inhibition of this calcium-sensitizing pathway results in blood vessel relaxation. It is also possible that blockade of additional smooth muscle contractile signaling mechanisms may have the same effect. In this review, we conducted an extensive search of pertinent literature using PUBMED. We have outlined the various pathways involved in the maintenance of penile smooth muscle tone and discussed the current potential benefit for the pharmacological inhibition of these targets for the treatment of ED.

Erectile Dysfunction in Men on the Rise: Is There a Link with Endocrine Disrupting Chemicals?

“…7) [Li et al, 1998;Nunes et al, 2010]. CPI-17 is expressed in the human and rabbit corpus cavernosum, although to the best of our knowledge, smooth muscle contraction in the penis mediated by PKC/CPI-17 signalling has yet to be proven [Jiang and Chitaley, 2012]. However, exposure of the rat corpus cavernosum to phorbol 12-myristate13-acetate (PMA) (PKC activator) potentiates phenylephrine-induced contractions in vitro, while exposure to chelerythine chloride (PKC inhibitor) inhibits it [Husain et al, 2004].…”