Role of angiotensin II and free radicals in blood pressure regulation in arat model of renal hypertension

One-kidney, 1-clip rats (1K1C) or uninephrectomized controls were treated w ith either the superoxide dismutase mimetic tempol (0.5 mmol . kg(-1) . d(- 1)), angiotension type 1 receptor inhibitor losartan (50 mmol . L-1 . kg(-1 ) . d(-1)), or both (n=6 per group) for 2 weeks. At the end of the study, s ystolic blood pressure (BP) decreased on average by 21% in tempol-treated a nd 29% in losartan-treated versus untreated 1K1C (217+/-4.4 mm Hg) and was normalized in the losartan plus tempol group. Mean BP also decreased from 1 59+/-3.7 mm Hg in 1K1C to 93+/-2.8 mm Hg in the losartan plus tempol group. Also, aortic wall area was reduced by 18% in losartan- or tempol-treated 1 K1C and by 30% in losartan plus tempol rats compared with untreated 1K1C. P lasma renin activity was increased from 4.8+/-0.3 in untreated 1K1C to 15.9 +/-0.9 ng . mL(-1) . h(-1) in losartan-treated but not tempol-treated 1K1C. Superoxide generation by the isolated aortic rings assessed by lucigenin c hemiluminescence was significantly decreased (by approximate to 40%) in all losartan, tempol, and losartan plus tempol groups compared with untreated 1K1C. Nitrotyrosine ELISA in the kidney displayed a significant reduction, from 59+/-13 ng/mg of protein in 1K1C to 12.5+/-5 ng/mg of protein in the l osartan plus tempol 1K1C. Western blotting for nNOS in kidney cortex and me dulla showed a protein increase in both fractions of 1K1C versus controls a nd was normalized by losartan plus tempol treatment. Collectively, data sho w a synergistic effect of losartan and tempol on BP reduction in 1K1C rats. The mechanism may involve reduced superoxide production and nitrotyrosine formation in kidney and decreased kidney neuronal-type NO synthase expressi on in treated animals. This status in the oxidative balance seems to affect BP in the renal hypertensive rats.