1017 ADRENOMEDULLIN AND ANGIOPOIETIN-1 HAVE A INTEGRATED RESTIRATION ACTIVITY ON ERECTILE FUNCTION IN DIABETIC RATS: COMPARISON WITH THE COMBINATION THERAPY WITH VASCULAR ENDOTHELIAL GROWTH FACTOR AND ANGIOPOIETIN-1

Abstract

ity are still unclear. The objective of this work was to evaluate the effects of partial bladder outlet obstruction (PBOO) on function of sensory terminals innervating the corpus cavernosum (CC), and release of sensory neuropeptides Substance P (SP) and calcitonin gene related peptide (CGRP) in the CC using an animal model of PBOO. METHODS: Experiments were conducted on adult male Sprague Dawley rats divided into two groups: sham operated and PBOO surgery. PBOO was surgically induced by a partial ligation of the bladder neck during laparotomy. Concentration of the sensory neuropeptides SP and CGRP was measured by ELISA. Contractility and relaxation of the CCSM was studied in vitro and expression of nitric oxide synthase (NOS) was evaluated by Western blotting. RESULTS: The results of neuropeptide analysis established that the release of SP and CGRP in the pelvic viscera is tissue dependent. Concentration of SP in the CC was higher (2.01 0.23 ng/ml, n 10) in comparison to the urinary bladder (0.3 0.05 ng/ml, n 8, p 0.001) under normal physiological conditions. However, basal concentration of CGRP was significantly elevated in the urinary bladder reaching 120.6 37.2 pg/ml in comparison to 14.5 0.9 pg/ml in the CC (p 0.01). PBOO caused impairment in SP release from sensory terminals as evidenced by a 5-fold down-regulation of SP in the CC (n 10, p 0.001) without significant changes in the obstructed bladder. Additionally, concentration of CGRP was down-regulated in the urinary bladder by PBOO without parallel changes in the CC, however, the decrease did not reach the level of statistical significance. The contractile responses of CC muscle strips to KCl and phenylephrine were decreased after PBOO, followed by a reduced relaxation response to nitroprusside. A significant decrease in nNOS expression was also detected in the CC of obstructed animals. CONCLUSIONS: Our results provide evidence that PBOO leads to the impairment of bladder neck afferent innervation followed by a decrease in CC smooth muscle relaxation, down-regulation of nNOS expression and reduced release of sensory neuropeptides in the CC smooth muscle. These results suggest that nerve damage in PBOO may contribute to LUTS-ED comorbidity and trigger secondary changes in the contraction/relaxation mechanisms of CCSM.