Vasoprotective and Atheroprotective Effects of Angiotensin (1-7) in Apolipoprotein E–Deficient Mice

Abstract

Long-term Ang (1-7) treatment caused both vasoprotection, via improvement in endothelial function, and atheroprotection, with a reduction in lesion progression in a model of atherosclerosis. These effects appear to be mediated by the restoration of nitric oxide bioavailability and involve a complex interaction of both Mas and AT(2) receptors.

Angiotensin-(1-7) Protects against the Development of Aneurysmal Subarachnoid Hemorrhage in Mice

“…In a chronic setting, the athero-protective effect of Ang-(1-7) was abrogated by an AT2R antagonist. 18 These findings suggest a functional and possibly physical interaction between Mas receptor and AT2R in the vascular system. 11 We found that Ang-(1-7) reduced expression of IL-1β and TNF-α in cerebral arteries.…”

“…It can reduce vascular inflammation, oxidative stress, cell proliferation, and nitric oxide availability, thereby reducing atherosclerosis and enhancing plaque stability. 18,21 It possesses a high binding capacity to Mas receptor, a G proteincoupled receptor that appears to mediate many of the biologic effects of Ang-(1-7). 7,9 Although the binding affinity of AT2R with Ang-(1-7) is relatively weak, AT2R appears to mediate some of the vascular effects of Ang- (1-7).…”

“…13,14 By treating the mice with an experimental agent starting from 6 days after aneurysm induction, we were able to test whether the experimental agent could reduce the rupture rate. 13,14 Therefore, in this study, the treatments with Ang-(1-7) (0.5 mg/kg/day) 17,18 with or without a Mas receptor antagonist (A779 0.5 mg/kg/day or 2.5 mg/kg/day) 17,18 or an AT2R antagonist (PD 123319, 10 mg/kg/day) 18,19 were initiated 6 days after aneurysm induction and were continued for 2 weeks. Angiotensin-(1-7), A779, and PD 123319 were dissolved in phosphate-buffered saline and filled into osmotic mini pump (model 1002, Alzet, Cupertino, CA, USA).…”

“…As a next step, we assessed whether the protective effect of Ang-(1-7) required the Mas receptor and AT2R by treating 25 mice with Ang-(1-7) and a Mas receptor antagonist (A779) at 0.5 mg/kg/ day, the dose that has been successfully used in the previous studies, 17,18,20,21 and 25 mice with Ang-(1-7) and the Mas receptor antagonist a five-fold higher dose of (2.5 mg/kg/day). Two mice from each group were excluded because of intraoperative mortality.…”

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

“…21 However, whether Ang II receptors are involved in Ang-(1-7)-stimulated effects is still under debate because some of the stimulated pathways are also affected by co-treatment with AT 1 blockers 22,23 or AT 2 blockers. 24,25 To further characterize the impact of Ang II receptor subtypes on Ang-(1-7) mediated vascular relaxation, we investigated the cardiovascular response to acute Ang-(1-7) infusion in recently generated mice lacking one, two or all three Ang II receptor subtypes. 26 …”