Evidence that the vasodilator angiotensin-(1–7)-Mas axis plays an important role in erectile function
Copyright policy )Evidence that the vasodilator angiotensin-(1–7)-Mas axis plays an important role in erectile function
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−1potentiated 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 Nω-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.
- Helmholtz Association of German Research Centres Germany
- Georgia Regents University United States
- University of Ottawa Canada
- UNIVERSIDADE DE SAO PAULO Brazil
- Max Delbrück Center for Molecular Medicine Germany
Male, Mice, Knockout, Angiotensin II, Penile Erection, Nitric Oxide, Immunohistochemistry, Electric Stimulation, Peptide Fragments, Mice, Inbred C57BL, Disease Models, Animal, Mice, NG-Nitroarginine Methyl Ester, Erectile Dysfunction, Hypertension, Animals, Angiotensin I, Enzyme Inhibitors, Nitric Oxide Synthase, Desoxycorticosterone, Penis
Male, Mice, Knockout, Angiotensin II, Penile Erection, Nitric Oxide, Immunohistochemistry, Electric Stimulation, Peptide Fragments, Mice, Inbred C57BL, Disease Models, Animal, Mice, NG-Nitroarginine Methyl Ester, Erectile Dysfunction, Hypertension, Animals, Angiotensin I, Enzyme Inhibitors, Nitric Oxide Synthase, Desoxycorticosterone, Penis
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