MP47-14 PIOGLITAZONE IS PROTECTIVE AGAINST POST-PROSTATECTOMY ERECTILE DYSFUNCTION

Abstract

INTRODUCTION AND OBJECTIVES: Penile smooth muscle tone is finely tuned by neurogenic stimuli. Alteration of neurogenic regulation could cause an imbalance in favour of contractile stimuli and compromise erection. We have previously observed that calcium-activated potassium channel (KCa) stimulation enhances vasodilatory capacity of PDE5 inhibitors in human penile arteries. The aim of this work was to evaluate the impact of KCa modulation on the neurogenic regulation of cavernosal smooth muscle tone in rats and humans. METHODS: Rat corpus cavernosum (RCC) was obtained from thirty 12-16 weeks old male Sprague-Dawley rats. Human corpus cavernosum (HCC) strips were obtained from 20 patients with erectile dysfunction (ED) who gave informed consent at the time of penile prosthesis implantation. RCC and HCC were mounted in organ chambers and responses to electrical field stimulation (EFS) were evaluated. RESULTS: EFS caused reproducible, frequency-dependent contractions in RCC. Blockade of KCa with tertaethylammonium (TEA) markedly potentiated neurogenic contractions (16Hz, 67.2 3.2% vs. 105.6 4.6% at 5mM, p<0.001) but did not modify norepinephrineinduced contractions. By using specific KCa subtype blockers, largeconductance KCa (BK) appeared as responsible for modulation of neurogenic contractions. Stimulation of BK with NS1619 significantly inhibited EFS-induced contractions in RCC (67.5 5.4% vs. 39.3 5.8%, p<0.01 at 30mM). BK stimulation also caused a significant potentiation of EFS-induced relaxations in phenylephrine-contracted RCC treated with guanethidine and atropine (2 Hz, 31.8 6.9% vs. 64.9 6.7%, p<0.01). Similar results were obtained in HCC where TEA caused concentration-dependent enhancement of EFS-induced contractions (35.3 3.4% vs. 118.5 32.0% at 5mM, p<0.01) while BK activation with NS1619 (30mM) inhibited neurogenic contractions and potentiated neurogenic relaxations. CONCLUSIONS: BK participates in regulation of neurogenic control of cavernosal smooth muscle tone. Pharmacological stimulation of these channel would favor relaxant responses over contractile input in rat and human cavernosal tissue. Thus, BK stimulation could be a reasonable strategy for treating ED mainly in situations involving imbalanced regulation of neurogenic control.