title: Evidence that the vasodilator angiotensin-(1-7)-Mas axis plays an important role in erectile function.
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 x kg(-1) x 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(omega)-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.
authors.affiliation: Department of Physiology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Andrey C
authors.initials: AC
authors.lastname: da Costa Gonçalves
authors.forename: Romulo
authors.initials: R
authors.lastname: Leite
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Fraga-Silva
authors.forename: Sergio V
authors.initials: SV
authors.lastname: Pinheiro
authors.forename: Augusto B
authors.initials: AB
authors.lastname: Reis
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Reis
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology* / Q000627:therapeutic use; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017673:Sodium Chloride, Dietary; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C092006:7-Ala-angiotensin (1-7); D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D017673:Sodium Chloride, Dietary; D014665:Vasodilator Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D000803:Angiotensin I; D019001:Nitric Oxide Synthase; C118790:angiotensin I (1-7); D019331:NG-Nitroarginine Methyl Ester