Abstract P281: Alamandine-induced Vasorelaxation is Selectively Increased in Sp-shr

Abstract

The renin angiotensin system is implicated in hypertension and cardiovascular diseases. It’s actions are dependent of counter-regulatory modulation of its vasopressor and vasodepressor axes. Recently, our laboratory described and characterized a new component the RAS, alamandine and its receptor, the MrgD. Alamandine can be formed from angiotensin A through the action ACE2 or from angiotensin-(1-7), by a still unknown decarboxylase. Among the actions of alamandine, a endothelium-dependent vasorelaxation in aortic rings of mice and rats has been described. The aim of this study was to investigate the vasorelaxing effect of alamandine in aortic rings of hypertensive rats. The vasorelaxing effect of alamandine was tested in aortic rings taken from SP-SHR, Wistar and SHR, pre-contracted with phenylephrine (0.1 μM) with and without enthotelium or in the presence of L-Name (100 μM ) or Indomethacin ( 10 μM). In aortic rings from SP-SHR alamandine produced a pronounced dose-dependent relaxation when compared with Wistar (Emax= 80± 6,0 vs 45 ± 4). This response was diminished in the presence of L-Name (Emax= 39 ± 7 in SP-SHR and 1,0 ± 3 in Wistar). Indomethacin also attenuated the vasorelaxation produced by alamandine in aortic rings from SP-SHR (Emax = 40 ± 4,0), while a smaller effect was observed in Wistar rats (Emax= 31 ± 4). The vasorelaxing effect of alamandine in SP-SHR was abolished in endothelium desnude rings (Emax= -9 ± 4). When we compare two models of animals with hypertension, SHR-SP and SHR the vasorelaxing effect of alamandine was also more pronounced in SP-SHR ( Emax = 80± 6,0 and 38 ± 4 respectively).Taken together these results suggest that the vasorelaxing effect of alamandine is selectively increased in SP-SHR. The mechanism of it effect in SP-SHR appears to involve NO and prostaglandins release.