Title: Abstract P111: Cross-Inhibition of the Vasorelaxing Effect of Ang-(1-9) and Ang-(1-7) in Aortic Rings
Abstract: Angiotensin-(1-9) is a nonapeptide formed by the hydrolysis of angiotensin I by ACE2 that seems to counter-regulate the classical RAS axis. The effect produced by Ang-(1-9), has an important role in the cardiovascular system promoting effects similar to those of Ang-(1-7). As vasodilation, anti-hypertrophic action in cardiomyocytes and antihypertensive effect. Because it has been reported that the Ang-(1-9) effects are independent of the Ang-(1-7) receptor Mas, in this study we investigated a possible synergistic additive effect of Ang-(1-9) and Ang-(1-7) in aortic rings. Materials and methods: The endothelium-dependent vasodilatory response to Ang-(1-7) and Ang-(1-9) (10-10 - 10-6 moles/l) alone or in combination was tested in aortic rings taken from Sprague-Dawley rats, pre-contracted with phenylephrine (0.1 umoles/L). Results: In aortic rings from SD rats, Ang-(1-7) and Ang-(1-9) induces vascular relaxation (Emax= 13.8±4.5% and 15±2.5%, n=5, respectively). Interestingly, pre-incubation with Ang-(1-9) abolished the vasodilatation induced by Ang- (1-7) (Emax= -2.7 ±1.4%, n=5). Likewise, pre-incubation with Ang-(1-7) abolished the vasorelaxation induced by Ang- (1-9). Indeed in aortic rings pre-incubated with Ang-(1-7),addition of Ang-(1-9) induced contraction instead of relaxation of the aortic rings (Emax= -10±1.7%, n=5). To test the effect of acute combination of the peptides in aortic rings, Ang-(1-7) was prepared in a 10-7M solution of Ang-(1-9) or vice-versa. As observed with pre-incubetion, the vasodilator effect induced by Ang (1-7) or Ang-(1-9) was abolished (Emax= -2.9±2.6 %, n=6 and 4±1.3%, n=6, respectively). These results suggest that these two peptides counter-regulate the vascular effects of each other. Whether these phenomenon in due to receptor internalization or to a signaling-related mechanism, remain to be clarified.
Publication Year: 2015
Publication Date: 2015-09-01
Language: en
Type: article
Indexed In: ['crossref']
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