Enhanced vasorelaxation effect of endogenous anandamide on thoracic aorta in renal vascular hypertension rats

Abstract

Summary Emerging evidence has indicated that anandamide (AEA) is able to stimulate vasorelaxation in both spontaneously hypertensive rats (SHRs) and L ‐NAME‐induced hypertensive rats. Yet it remains unknown whether AEA modulates vasomotion of the aorta in renovascular hypertensive (RVH) rats. The aim of present study is to explore the effect of AEA on the relaxation of thoracic aortas in two‐kidney one‐clip (2K1C)‐induced RVH rats. It is demonstrated that AEA stimulates a pronounced relaxation in the aortas of 2K1C rats compared with sham rats. The enhanced relaxation caused by AEA in aortas from 2K1C rats was diminished in the presence of the cannabinoid receptor‐1 (CB 1 ) antagonist AM251 and the CB 2 receptor antagonist AM630. Likewise, the vasodilation action of AEA was blocked in L ‐NAME‐treated or endothelium‐denuded aortas. The Western blot results revealed that the expression of CB 1 and CB 2 receptors was increased in the 2K1C rat aortas compared with sham rats. The phosphorylation of endothelial nitric oxide synthase (p‐eNOS) at the activation site Ser1177 was enhanced in AEA‐treated rings from 2K1C rats in both time‐dependent and dose‐dependent manners. The augmented p‐eNOS expression was inhibited by the co‐treatment with AM251 or AM630. Taken together, the present study demonstrated that AEA enhanced endothelium‐dependent aortic relaxation through activation of both CB 1 and CB 2 receptors and P‐eNOS/NO pathway in 2K1C rats.