Endogenous hydrogen peroxide up-regulates the expression of nitric oxide synthase in the kidney of SHR

Abstract

Both nitric oxide synthase (NOS) expression and oxidative stress are elevated in the tissues of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). The purpose of the present study was to determine the relationship between the endothelial and neuronal NOS (eNOS and nNOS) expression and oxidative stress in the kidney of SHR and WKY. Plasma and urinary hydrogen peroxide (H₂O₂) and nitrate/nitrite (NOx), the renal NADPH oxidase activity and eNOS and nNOS expressions were all higher in SHR than in WKY. Although the treatment with either the NADPH oxidase inhibitor, apocynin or the superoxide dismutase mimetic, tempol for 8 weeks decreased the systolic blood pressure (SBP) and inhibited the renal NADPH oxidase activity in SHR, apocynin decreased but tempol increased the plasma and urinary H₂O₂ and NOx and the eNOS and nNOS expressions in the renal cortex and medulla of SHR. In contrast to SHR, neither apocynin nor tempol affected these parameters in WKY. H₂O₂ administered intravenously for 1 week in WKY increased plasma and urinary H₂O₂ and NOx and the eNOS and nNOS expressions in the renal cortex and medulla in a dose-dependent manner without changing the renal NADPH oxidase activity. These results indicate that oxidative stress up-regulates the NOS expression in the kidney of SHR compared with WKY; and that endogenous H₂O₂ is a mediator of the up-regulation of the NOS expression in the kidney of SHR.