Enhanced superoxide anion formation in vascular tissues from spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats

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Abstract
To investigate the basal and NADH-stimulated superoxide (⋅ O2 −) production and inactivation by Cu/Zn superoxide dismutase (SOD) in aorta from spontaneously hypertensive rats (SHR) and from desoxycorticosterone acetate (DOCA)-salt hypertensive (DOCA-HT) rats. Tissue ⋅ O2 − levels were estimated with the lucigenin-enhanced chemiluminescence method in aorta and cultured smooth muscle cells (SMCs) from SHR and in aorta from DOCA-HT rats treated for 4 weeks. The basal aortic ⋅ O2 − generation was increased by 135 and 100%, and the NADH stimulated ⋅ O2 − production was also increased 37 and 22% in SHR and in DOCA-HT rats compared to their normotensive controls, respectively. Although no difference existed in blood pressure as well as in basal and in NADH stimulated ⋅ O2 − production between Wistar–Kyoto (WKY) rats and SHR rats at age of 6 weeks, O2 − production and blood pressure increased concomitantly in SHR aged 9 and 12 weeks. Basal and NADH-stimulated ⋅ O2 − production, in cultured SMCs, was also 80 and 64% higher, respectively, in SHR compared to WKY rats. The NADH oxidase activity was found to be increased in aorta from both SHR and DOCA-HT rats but SOD activity was reduced only in aorta from DOCA-HT rats. An enhanced ⋅ O2 − formation resulting from an increased NADH oxidase activity was found in aorta from SHR and DOCA-HT rats. Cultured arterial SMCs from SHR also generated excessive ⋅ O2 − formation under basal and stimulated conditions. The age-related increase in vascular ⋅ O2 − formation in association with the rise in blood pressure in SHR suggests that the oxidative stress might contribute to the development of hypertension. NADH oxidase activity was greater in aorta of both hypertension models, but a decrease of Cu/Zn SOD activity could also contribute to the high level of aortic ⋅ O2 − in DOCA-HT rats.