AVE 0991, a non-peptide Mas-receptor agonist, facilitates penile erection

作者：da Costa Goncalves Andrey C; Fraga Silva Rodrigo A; Leite Romulo; Santos Robson A S^*

来源：Experimental Physiology, 2013, 98(3): 850-855.

DOI：10.1113/expphysiol.2012.068551

New findings center dot What is the central question of this study? The reninangiotensin system plays a crucial role in erectile function. While angiotensin II contributes to the development of erectile dysfunction, angiotensin-(17) mediates penile erection by activation of the Mas receptor. However, because of its peptidic nature, angiotensin-(17) is not resistant to proteolytic enzymes, thus limiting its clinical applications. In this study, we have hypothesized that the synthetic non-peptide Mas agonist, AVE 0991, would potentiate the penile erectile function. center dot What is the main finding and its importance We demonstrated that AVE 0991 potentiates the rat penile erectile response through Mas in a nitric oxide-dependent manner; therefore, our results suggest Mas agonists as potential targets for the treatment of erectile dysfunction. The reninangiotensin system plays a crucial role in erectile function. It has been shown that elevated levels of angiotensin II contribute to the development of erectile dysfunction both in humans and in aminals. On the contrary, the heptapeptide angiotensin-(17) appears to mediate penile erection by activation of the Mas receptor. Recently, we have shown that the erectile function of Mas gene-deleted mice was substantially reduced, which was associated with a marked increase in fibrous tissue in the corpus cavernosum. We have hypothesized that the synthetic non-peptide Mas agonist, AVE 0991, would potentiate penile erectile function. We showed that intracavernosal injection of AVE 0991 potentiated the erectile response of anaesthetized Wistar rats, measured as the ratio between corpus cavernosum pressure and mean arterial pressure, upon electrical stimulation of the major pelvic ganglion. The facilitatory effect of AVE 0991 on erectile function was dose dependent and completely blunted by the nitric oxide synthesis inhibitor, l-NAME. Importantly, concomitant intracavernosal infusion of the specific Mas receptor blocker, A-779, abolished the effect of AVE 0991. We demonstrated that AVE 0991 potentiates the penile erectile response through Mas in an NO-dependent manner. Importantly, these results suggest that Mas agonists, such as AVE 0991, might have significant therapeutic benefits for the treatment of erectile dysfunction.

• 出版日期2013-3