Effects of Sildenafil, a Phosphodiesterase Type 5 Inhibitor, on the Primary Single Afferent Activity of the Rat Bladder.

Abstract

We investigated the direct effects of sildenafil, a phosphodiesterase type 5 inhibitor, on the single-unit mechanosensitive afferent activities (SAAs) primarily originated from the bladder in the rat. Female Sprague-Dawley rats were anesthetized with urethane. SAAs were recorded from the left L6 dorsal roots and classified by conduction velocity as Aδ- or C-fibers. A catheter was inserted into the bladder dome, and a separate catheter was placed in the carotid artery and external iliac vein for monitoring of blood pressure and sildenafil-administration, respectively. After measuring control SAA during constant filling cystometry with saline, the procedure was repeated with cumulative intravenous administrations of sildenafil (1, 3 and 10 mg/kg). Thirteen single units were isolated (Aδ-fibers: n = 6, C-fibers: n = 7) from 11 rats. After sildenafil-administrations, SAAs of Aδ-fibers significantly decreased in a dose-dependent manner, whereas SAAs of C-fibers decreased significantly only at the highest dose used. In addition, blood pressure significantly decreased after sildenafiladministration even at the lowest dose used. Bladder compliance significantly increased after sildenafil administration at higher doses. These results indicate that sildenafil can inhibit Aδ-fibers (partly also C-fibers) of the primary bladder mechanosensitive afferents of the rat although these effects may be partially influenced by systemic hypotension. The present results support the view that the NO/cGMP signaling pathway plays an inhibitory role in the bladder afferent transduction, and thus improves storage symptoms.