Role of Arginases in the Angiotensin II-Induced Hypertension-Associated Endothelial Dysfunction in the Rat Aorta

Abstract

Increases in arginase activity have been reported in a variety of diseases associated with vascular dysfunction. As arginases compete with NO synthase for their common substrate L-arginine, an increased arginase activity might decrease the bioavailability of nitric oxide (NO), a major vasoprotective factor. Moreover, red wine polyphenols (RWPs) have been shown to prevent the endothelial dysfunction in several rat models, at least in part, through protection of NO bioavailability. The aim of the present study was to determine whether an increased arginase activity contributes to the Ang II-induced hypertension-associated endothelial dysfunction in the rat aorta, and, if so, to determine the protective effect of RWPs. Rats received either RWPs (150 mg/kg/day) or apocynin, an antioxidant and an inhibitor of NADPH oxidase (100 mg/kg/day), in the drinking water for 7 days before the infusion of Ang II (0.4 mg/kg/day) for 14 days. Arterial pressure was measured in conscious rats. After euthanasia, vascular reactivity was assessed in organ chambers, arginases activity by a colorimetric assay, and expression level of arginases by immunofluorescence. Ang II-induced hypertension is associated with an endothelial dysfunction characterized by a reduced relaxation and an increased contraction in response to acetylcholine. Moreover, Ang II infusion increased both expression and activity of arginases. Treatment with RWPs and apocynin prevented the Ang II-induced hypertension and endothelial dysfunction, and the associated increased arginase expression and activity. Altogether, these findings suggest that Ang II-induced hypertension and endothelial dysfunction are associated with an increased expression and activity of vascular arginases, which can be prevented by RWPs and apocynin. These results constitute a real contribution in the understanding of the physiopathology of endothelial dysfunction arterial high blood pressure induced by the angioyensine II. Besides, they offer real perspectives in prevention treatment of these cardiovascular disorders.