Sialorphin (the mature peptide product of Vcsa1) relaxes corporal smooth muscle tissue and increases erectile function in the ageing rat

Abstract

To determine if the mature peptide product of the Vcsa1 gene, sialorphin, could restore erectile function in ageing rats, and whether these effects are mediated through relaxation of corporal smooth muscle tissue, as we recently reported that Vcsa1 is one of the most down-regulated genes in the corpora of rats in three distinct models of erectile dysfunction, and gene transfer of plasmids expressing Vcsa1 into the corpora of ageing rats restored erectile function. Sialorphin was injected intracorporeally into retired breeder rats, and the effect on the physiology of corporal tissue was analysed by intracorporal/blood pressure (ICP/BP) measurement at different times after injection. In organ-bath studies, the ability of sialorphin (1 microg/mL) to enhance C-type natriuretic peptide (CNP) relaxation of corporal smooth muscle tissue strips was investigated after pre-contraction with 1 microm phenylephrine. Intracorporal injection of 100 microg sialorphin into retired breeder rats resulted in a time-dependent increase in the ICP/BP response to electrostimulation of the cavernosal nerve. After 55-65 min the ICP/BP ratio increased to approximately 0.6, a value associated with normal erectile function. In organ-bath studies after pre-contraction with 1 microm phenylephrine, 1 microm CNP significantly (67%) increased the relaxation rate of corporal tissue. This rate of relaxation was increased by 2.5-fold after incubation with sialorphin (1 microg/mL) compared with carrier alone. These results show that sialorphin has a role in erectile function, probably through a mechanism that involves relaxation of corporal smooth muscle tissue.