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

• Published in: American journal of physiology. Heart and circulatory physiology 2007-10, Vol.293 (4), p.H2588-H2596
• Main Authors: da Costa Goncalves, Andrey C, Leite, Romulo, Fraga-Silva, Rodrigo A, Pinheiro, Sergio V, Reis, Augusto B, Reis, Fernando M, Touyz, Rhian M, Webb, R. Clinton, Alenina, Natalia, Bader, Michael, Santos, Robson A. S
• Format: Article
• Language: English
• Subjects: Amino acids; Angiotensin I - pharmacology; Angiotensin I - therapeutic use; Angiotensin II - analogs & derivatives; Angiotensin II - pharmacology; Animals; Desoxycorticosterone; Disease Models, Animal; Electric Stimulation; Enzyme Inhibitors - pharmacology; Erectile Dysfunction - drug therapy; Erectile Dysfunction - etiology; Erectile Dysfunction - metabolism; Erectile Dysfunction - physiopathology; Hypertension - chemically induced; Hypertension - complications; Hypertension - metabolism; Hypertension - physiopathology; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Penile Erection - drug effects; Penis - drug effects; Penis - enzymology; Penis - innervation; Penis - metabolism; Peptide Fragments - pharmacology; Peptide Fragments - therapeutic use; Peptides; Proteins; Proto-Oncogene Proteins - deficiency; Proto-Oncogene Proteins - drug effects; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Rats; Rats, Wistar; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - drug effects; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Reproductive system; Rodents; Sodium Chloride, Dietary; Vasodilator Agents - pharmacology; Vasodilator Agents - therapeutic use
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00173.2007

1 Department of Physiology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2 Department of Physiology, Medical College of Georgia, Augusta, Georgia; 3 Surgery Department, Medical School of Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 4 Gynecology and Obstetrics Department, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 5 Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ontario, Canada; and 6 Max-Delbrück Center for Molecular Medicine, Berlin, Germany Submitted 11 February 2007 ; accepted in final form 5 July 2007 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 -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. renin-angiotensin system; nitric oxide; Mas receptor; penile erection Address for reprint requests and other correspondence: R. A. Souza dos Santos, Departamento de Fisiologia e Biofísica, Av. Antonio Carlos, 6627-ICB-UFMG, 3127-901 Belo Horizonte, MG, Brasil