Vaso‐ and athero‐protective effects of Angiotensin (1‐7) and CGP42112 in apolipoprotein‐E deficient mice

Abstract

The aim of this study was to investigate the effects of Angiotensin (Ang) (1‐7), a Mas receptor agonist, and CGP42112, an AT2 receptor agonist, in a setting of atherosclerosis. All treatments were investigated using apolipoprotein E‐deficient (ApoE−/−) mice fed a high fat diet for 16 weeks, with chronic treatment administered in final 4 weeks via osmotic mini‐pumps. Treatments were either: saline (vehicle), Ang (1‐7) (24µg/kg/hr) or CGP42112 (1µg/kg/min) alone, as well each agonist in combination with either an AT2R antagonist, PD123329 (10mg/kg/day), or the MasR antagonist, A779 (48µg/kg/hr). Chronic treatment with either Ang (1‐7) or CGP42112 significantly improved endothelial function and decreased lesion development compared to vehicle treated mice. Superoxide levels were significantly reduced and eNOS expression increased with Ang (1‐7) and CGP42112 treatments when compared to vehicle treated mice. Ang (1‐7) effects were reversed with both AT2R and MasR blockede, however, CGP42112 mediated effects were only reversed by the AT2R antagonist. This study indicates that both Ang (1‐7) and CGP42112 improve endothelial function and reduce atherosclerotic lesions via either the AT2 or the Mas receptor, or both. This highlights the importance of gaining a better understanding of the role of AT2 and Mas receptors in atherosclerosis.NHMRC (Australia)