Abstract 483: Mas/AT2 Receptor Deficient Mice Present A Pronounced Endothelial Dysfunction That Is Exclusively Mas-Related

Abstract

The angiotensin type 2 (AT2) receptor and the angiotensin-(1-7) receptor MAS belong to the protective arm of the Renin Angiotensin System (RAS). They behave in a very similar way in terms of their physiological (tissue-protective) actions. Here we evaluate the endothelial function of Mas/AT2 double knockout mice (DKO) in two different backgrounds, C57BL/6 and FVB/N-C57BL/6 mixed background. Endothelial function in conscious mice was evaluated by measuring changes in mean arterial pressure (MAP) in response to bolus intra-aortic acetylcholine (ACh) and sodium nitroprusside (SNP) administration. The substances were given in 1μL per 10 g of body weight at the following doses: 25, 50, 100 ng/kg for ACh and 10 μg/kg for SNP. To correct the differences in vascular smooth muscle reactivity, the response to ACh was normalized by the SNP response. Our main results show that regarding the absolute response to ACh, Mas/AT2 DKO animals in both backgrounds had markedly decreased vasodilation response when compared with wild type (WT) over the dose range of 25 to 100 ng/kg (table 1). The MasKO animals had similar impairment of the vasodilatory response as the DKO mice when compared with WT animals, thus there was no statistical difference between the MasKO and DKO animals. No significant difference between the AT2KO and WT animals was observed in regard to the vasodilatory response to ACh. Normalization of ACh response with the SNP effect reinforced the observation that endothelium-dependent vascular reactivity was impaired. The evidence provided in this study suggests that the endothelial dysfunction observed in the Mas/AT2 DKO animals is exclusively due to the deletion of Mas.