REPEATED PGE1 TREATMENT ENHANCES NITRIC OXIDE AND ERECTION RESPONSES TO NERVE STIMULATION IN THE RAT PENIS BY UPREGULATING CONSTITUTIVE NOS ISOFORMS

Abstract

To assess whether intracavernosal injections of prostaglandin E1 (PGE1) can influence nitric oxide (NO) release in the corpora in a rat model of penile erection. The extracellular levels of NO were monitored at 100 seconds intervals in the corpus cavernosum of anesthetized rats by using differential normal pulse voltammetry with porphyrin-Nafion coated carbon fiber microelectrodes. The intracavernosal pressure (ICP) was simultaneously recorded. PGE1 was given either as a single dose (ranging from 0.2 to 15 microg.) or as repeated 2 microg. injections in alternate days for two weeks. The NO and ICP responses to electrostimulation of the cavernosal nerve (SCN) was studied in the animals in the repeated treatment schedule at 1, 7, 15 and 30 days after its termination. The levels of the three NO synthase (NOS) isoforms in the cavernous tissue were measured by immunoblotting. Acute PGE1 treatment dose-relatedly increased NO levels in the corpora, with a concomitant ICP increase with the highest dose. Repeated 2 microg. PGE1 injections increased the NO and ICP responses to SCN as compared with intact or vehicle-injected animals. This treatment also increased the penile content of the neuronal and endothelial NOS proteins. The inducible NOS isoform remained unchanged after either vehicle or PGE1 injections. The effects of the repeated PGE1 treatment were greater in the group studied 24 hours after the last injection and decreased progressively thereafter. Stimulation of NO release can contribute to the erectogenic effect of intracavernous PGE1 injections. The increased levels of constitutive NOS isoforms in the corpora could contribute to the improvement of the erectile function reported by some patients following repeated treatment with vasorelaxant agents.