Influence of the angiotensin-(1-7) on the vascular effects of the endothelin-1 in normotensive and hypertensive rats.

Angiotensin-(1-7) [Ang-(1-7)] exerts cardioprotective effects through Mas receptor activation. Endothelin-1 (ET-1) is implicated in cardiovascular pathologies. Previous studies indicate a cross-talk between angiotensin and endothelin pathways; however, it remains unclear whether Ang-(1-7) differentially modulates vascular responses to ET-1 in normotensive and hypertensive conditions. This study investigated the influence of Ang-(1-7) on ET-1-induced pressor and vascular responses in normotensive and hypertensive rats (SHR). Blood pressure was recorded in conscious animals. Vascular reactivity was assessed in isolated aortic rings, and coronary effects were assessed in isolated hearts using the Langendorff technique. ET-1 increased blood pressure and reduced heart rate only in Wistar rats, effects abolished by Ang-(1-7). In normotensive rats, Ang-(1-7) potentiated ET-1-induced vasoconstriction in endothelium-intact aortas independently of Mas receptors, but had no effect in the aorta without endothelium. In hypertensive rats, Ang-(1-7) attenuated ET-1 responses in endothelium-intact aorta via Mas receptor, whereas in endothelium-denuded vessels it potentiated the vasoconstriction. In isolated hearts, ET-1 produced a biphasic response in normotensive rats (vasodilation followed by vasoconstriction) but only vasoconstriction in hypertensive rats. Ang-(1-7) potentiated vasoconstriction in normotensive but attenuated it in hypertensive hearts, which was abolished by Mas receptor blockade. These findings demonstrate that Ang-(1-7) differentially modulates ET-1 actions in normotensive and hypertensive conditions, reinforcing RAS-endothelin cross-talk. Its counter-regulatory effect in hypertension highlights Ang-(1-7) as a promising therapeutic target in cardiovascular disease.