Molecular mechanisms of angiotensin type 2 receptor-mediated nitric oxide pathway in angiotensin II-induced vasorelaxation: Roles of potassium channels.

A variety of biological functions is attributed to the renin-angiotensin system (RAS). One of them is regulating vascular tone through its final effector Angiotensin II (Ang II). Ang II action is mediated by the Angiotensin type 1 receptor (AT1-R) which plays a role in vasoconstriction, and Angiotensin type 2 receptor (AT2-R) which may result in vascular relaxation through the releasing of endothelium mediates relaxation factors such as Nitric Oxide (NO). Therefore, this study investigated the role of AT2-R in vasodilation after blocking the effect of AT1-R in the rat aorta. Furthermore, it is to determine whether or not Ang II through NO has a role in rat aorta dilation via using valsartan. For control isolated aortic rings were preincubated with Valsartan (AT1- R inhibitor) and then stimulated with angiotensin II dose-dependent. For treating aortic rings different blockers and inhibitors were used. Pd123177 (AT2- R inhibitor) (20 µM), an inhibitor of PKA H-89 (10 µM), eNOS inhibitor L-NAME (0.3 mM), with group of K channel blockers such as TEA (1 mM), 4-AP (1 mM), BaCl2 (1 mM), clotrimazole (0.03 mM) and GLIB (0.01 mM). Our analysis demonstrates vasodilation in aortic rings induced by Ang II after blocking ATI-R and this response was highly reliant on PKA/eNOS and cyclic guanosine monophosphate (cGMP). The data from this investigation provided evidence that Ca2 + activated K+ channels (KCa) and Voltage-dependent K channel (KV) mediated Ang II vasorelaxation. Finally, these results indicate that angiotensin II primarily induces dilatation AT2-R after inhibiting the angiotensin AT1 receptor through a cascade of signaling pathways involving many enzymes and plasma membrane protein channels.