Endothelial dysfunction in DOCA-salt hypertensive mice: Role of neuronal nitric oxide synthase-derived hydrogen peroxide

Endothelial dysfunction is a common problem associated with hypertension and is considered a precursor to the development of micro- and macrovascular complications. The present study investigated the involvement of neuronal nitric oxide synthase (nNOS) and hydrogen peroxide (H2O2) in the impaired endothelium-dependent vasodilation of the mesenteric arteries of DOCA-salt hypertensive mice (DOCA-salt). Myograph studies were used to investigate the endothelium-dependent vasodilator effect of acetylcholine (ACh). The expression and phosphorylation of nNOS and endothelial NOS (eNOS) were studied by western blot analysis. Immunofluorescence was used to examine the localization of nNOS and eNOS in the endothelial layer of the mesenteric artery. The vasodilator effect of ACh is strongly impaired in mesenteric arteries of DOCA-salt. Non-selective inhibition of NOS sharply reduced the effect of ACh in both DOCA-salt and sham mice. Selective inhibition of nNOS and catalase led to a higher reduction in the effect of ACh in sham than in DOCA-salt. Production of H2O2 induced by ACh was significantly reduced in vessels from DOCA-salt, and it was blunted after nNOS inhibition. The expressions of both eNOS and nNOS were considerably lower in DOCA-salt while phosphorylation of their inhibitory sites was increased. The presence of nNOS was confirmed in the endothelial layer of mesenteric arteries from both sham and DOCA-salt. These results demonstrate that endothelial dysfunction in the mesente...

Source: Clinical Science - March 14, 2016 Category: Biomedical Science Authors: Silva, G. C., Silva, J. F., Diniz, T. F., Lemos, V. S., Cortes, S. F. Tags: PublishAheadOfPrint Source Type: research