Repeated PGE1 treatment enhances nitric oxide and erection responses to nerve stimulation in the rat penis by upregulating constitutive NOs isoforms

Purpose: To assess whether intracavernosal injections of prostaglandin El ( PGE1) can influence nitric oxide (NO) release in the corpora in a rat model of penile erection. Materials and Methods: The extracellular levels of NO were monitored at 100 seconds intervals in the corpus cavernosum of anesthetized rats by using d ifferential normal pulse voltammetry with porphyrin-Nafion coated carbon fi ber microelectrodes. The intracavernosal pressure (ICP) was simultaneously recorded. PGE1 was gives either as a single dose (ranging from 0.2 to 15 mu g.) or as repeated 2 mu g. injections in alternate days for two weeks. The NO and ICP responses to electrostimulation of the cavernosal nerve (SCN) w as studied in the animals in the repeated treatment schedule at 1, 7, 15 an d 30 days after its termination. The levels of the three NO synthase (NOS) isoforms in the cavernous tissue were measured by immunoblotting. Results: Acute PGE1 treatment dose-relatedly increased NO levels in the cor pora, with a concomitant ICP increase with the highest dose. Repeated 2 mu g. PGE1 injections increased the NO and ICP responses to SCN as compared wi th intact or vehicle-injected animals. This treatment also increased the pe nile content of the neuronal and endothelial NOS proteins. The inducible NO S isoform remained unchanged after either vehicle or PGE1 injections. The e ffects of the repeated PGE1 treatment were greater in the group studied 24 hours after the last injection and decreased progressively thereafter. Conclusions: Stimulation of NO release can contribute to the erectogenic ef fect of intracavernous PGE1 injections. The increased levels of constitutiv e NOS isoforms in the corpora could contribute to the improvement of the er ectile function reported by some patients following repeated treatment with vasorelaxant agents.