Role of NADPH Oxidase in the Endothelial Dysfunction and Oxidative Stress in Aorta of Aged Spontaneous Hypertensive Rats

Objective(s) Increased reactive oxygen species (ROS) production is implicated in the pathogenesis of arterial hypertension and the development of endothelial dysfunction. NADPH oxidase type enzyme family has been suggested to form ROS and to interfere with endothelium-dependent relaxation. However, the specific isoform of NADPH oxidases that may predominantly contribute to these events remains to be clarified. Materials and Methods Here we investigated the expressional regulation of NADPH oxidase isoforms (NOX1, NOX2 and NOX4) in aorta of aged spontaneously hypertensive rats (SHR) in comparison to age matched Wistar Kyoto rats (WKY). Moreover, we examined the effect of in vitro inhibition of NADPH oxidase by apocynin or the novel NADPH oxidase inhibitor, VAS2870 on the vascular reactivity and ROS production. Results Our results showed that ROS formation was largely increased in aorta of SHR as measured by dihydroethidine (DHE) fluorescence and inhibited by apocynin or VAS2870. NADPH oxidase activity, measured by lucigenin-enhanced chemiluminescence and of NOX1 and NOX2 protein levels were increased in aortic homogenates from SHR compared to WKY. However, NOX4 protein expression was not significantly changed. Furthermore, the impaired acetylcholine-induced relaxation of SHR aorta was significantly improved in the presence of either apocynin or VAS2870. Conclusion Collectively, our data suggest that NADPH oxidases, particularly NOX1 and NOX2 are relevant sources of ROS in the aorta of aged SHR thereby cause endothelial dysfunction, and VAS2870 is effective as apocynin in reversing these consequences.