Evidence that the vasodilator angiotensin-(1-7)-Mas axis plays an important role in erectile function

Andrey C. Da Costa Gonçalves, Romulo Leite, Rodrigo A. Fraga-Silva, Sergio V. Pinheiro, Augusto B. Reis, Fernando M. Reis, Rhian M. Touyz, R. Clinton Webb, Natalia Alenina, Michael Bader, Robson A.S. Santos

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

The vasodilator/antiproliferative peptide angiotensin-(1-7) [ANG-(1-7)] is released into the corpus cavernosum sinuses, but its role in erectile function has yet to be defined. In this study, we sought to determine whether ANG-(1-7) and its receptor Mas play a role in erectile function. The ANG-(1-7) receptor Mas was immunolocalized in rat corpus cavernosum by confocal microscopy. Infusion of ANG-(1-7) into corpus cavernosum at a rate of 15.5 pmol · kg-1 · min-1 potentiated the elevation of the corpus cavernosum pressure induced by electrical stimulation of the major pelvic ganglion (MPG) in rats. The facilitatory effect of ANG-(1-7) was completely blunted by the specific ANG-(1-7) receptor blocker A-779 and N ω-nitro-L-arginine methyl ester. Nitric oxide (NO) release in the corpus cavernosum was evaluated with the fluorescent dye 4-amino-5 methylamino-2′,7′-difluorofluorescein diacetate. Electrical stimulated-release of NO in rat corpus cavernosum was potentiated by ANG-(1-7). Furthermore, incubation of rat and mouse corpus cavernosum strips with ANG-(1-7) at 10 nmol/l resulted in an increase of NO release. This effect was completely abolished in mas-deficient mice. More importantly, genetic deletion of Mas resulted in compromised erectile function as demonstrated by penile fibrosis and severely depressed response to electrical stimulation of the MPG. Furthermore, the attenuated erectile function of DOCA-salt hypertensive rats was fully restored by ANG-(1-7) administration. Together these data provide strong evidence for a key role of the ANG-(1-7)-Mas axis in erectile function.

Original languageEnglish (US)
Pages (from-to)H2588-H2596
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 1 2007

Keywords

  • Mas receptor
  • Nitric oxide
  • Penile erection
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Da Costa Gonçalves, A. C., Leite, R., Fraga-Silva, R. A., Pinheiro, S. V., Reis, A. B., Reis, F. M., Touyz, R. M., Webb, R. C., Alenina, N., Bader, M., & Santos, R. A. S. (2007). Evidence that the vasodilator angiotensin-(1-7)-Mas axis plays an important role in erectile function. American Journal of Physiology - Heart and Circulatory Physiology, 293(4), H2588-H2596. https://doi.org/10.1152/ajpheart.00173.2007