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

Abstract

One-kidney, 1-clip rats (1K1C) or uninephrectomized controls were treated with 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, systolic blood pressure (BP) decreased on average by 21% in tempol-treated and 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 159±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 1K1C and by 30% in losartan plus tempol rats compared with untreated 1K1C. Plasma 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 chemiluminescence was significantly decreased (by ≈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 losartan plus tempol 1K1C. Western blotting for nNOS in kidney cortex and medulla showed a protein increase in both fractions of 1K1C versus controls and was normalized by losartan plus tempol treatment. Collectively, data show 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 expression in treated animals. This status in the oxidative balance seems to affect BP in the renal hypertensive rats.