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

Item Type:Article
Title:AVE 0991, a non-peptide Mas-receptor agonist, facilitates penile erection
Creators Name:da Costa-Goncalves, A.C. and Fraga-Silva, R.A. and Leite, R. and Santos, R.A.S.
Abstract:The renin angiotensin system (RAS) plays a crucial role in erectile function. It has been shown that elevated angiotensin II levels contribute to the development of erectile dysfunction both in human and in aminals. On the other hand, the heptapeptide angiotensin-(1-7) appears to mediate penile erection by activation of receptor Mas. 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 the penile erectile function. To evaluate that, intracavernosal injection of AVE 0991 potentiates the erectile response of anesthetized Wistar rats, measured as corpus cavernosum pressure/mean arterial pressure (CCP/MAP) 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 (NO) 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 penile erectile response through Mas in a 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.
Keywords:Angiotensin, Angiotensin II, G-Protein-Coupled Receptors, Imidazoles, NG-Nitroarginine Methyl Ester, Nitric Oxide, Penile Erection, Peptide Fragments, Proto-Oncogene Proteins, Wistar Rats, Animals, Rats
Source:Experimental Physiology
Page Range:850-855
Date:March 2013
Official Publication:https://doi.org/10.1113/expphysiol.2012.068551
PubMed:View item in PubMed

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