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

Objectives To investigate the basal and NADH-stimulated superoxide (O-.(2)- ) production and inactivation by Cu/Zn superoxide dismutase (SOD) in aorta from spontaneously hypertensive rats (SHR) and from desoxycorticosterone ac etate (DOCA)-salt hypertensive (DOCA-HT) rats. Methods Tissue O-.(2)- levels were estimated with the lucigenin-enhanced ch emiluminescence method in aorta and cultured smooth muscle cells (SMCs) fro m SHR and in aorta from DOCA-HT rats treated for 4 weeks. Results The basal aortic O-.(2)- generation was increased by 135 and 100%, and the NADH stimulated, O-.(2)- production was also increased 37 and 22% i n SHR and in DOCA-HT rats compared to their normotensive controls, respecti vely Although no difference existed in blood pressure as well as in basal a nd in NADH stimulated, O-.(2)- production between Wistar-Kyoto (WKY) rats a nd SHR rats at age of 6 weeks, O-.(2)- production and blood pressure increa sed concomitantly in SHR aged 9 and 12 weeks. Basal and NADH-stimulated O-. (2)- production, in cultured SMCs, was 1also 80 and 64% higher, respectivel y, in SHR compared to WKY rats. The NADH oxidase activity was found to be i ncreased in aorta from both SHR and DOCA-HT rats but SOD activity was reduc ed only in aorta from DOCA-HT rats. Conclusions An enhanced O-.(2)- formation resulting from an increased NADH oxidase activity was found in aorta from SHR and DOCA-HT rats. Cultured art erial SMCs from SHR also generated excessive O-.(2)- formation under basal and stimulated conditions. The age-related increase in vascular O-.(2)- for mation in association with the rise in blood pressure in SHR suggests that the oxidative stress might contribute to the development of hypertension. N ADH 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 O-.(2)- in DOCA-HT rats. (C) 2001 Lippincott Williams & Wilkins.