ASSA14-03-13 Superoxide-lowering Therapy with Tempol Improves Balance of Renal RAS Components in Obese Zucker Rats

Objective Oxidative stress plays an important role in the pathogenesis of hypertension, particularly associated with obesity-related hypertension. Increased oxidative stress leads to an imbalance of the natriuretic and antinatriuretic factors of the renal renin angiotensin system (RAS). We hypothesise that superoxide-lowering therapy using tempol reverses this imbalance resulting to natriuresis and diuresis, thus lowering the blood pressure of obese Zucker rats. Methods Lean and obese Zucker rats received regular or antioxidant enzyme superoxide dismutase (SOD) mimetic tempol (1.0 mmol/l) in the drinking water for 4 weeks. Results Results showed that, compared with lean rats, obese rats exhibited higher blood pressures, higher levels of renal oxidative stress, accompanied by increased natriuretic responses to AT 1 R antagonist (candesartan) and AT 2 R agonist (CGP-42112A) and reduced natriuretic response to MasR agonist (ang-[1–7]). Moreover, obese rats had higher levels of ACE, AT 1 R and AT 2 R, lower levels of ACE2 and Mas receptors in the kidney. All of the above-mentioned abnormalities were reversed to some degree by tempol treatment. Conclusion Our study indicates that superoxide-lowering therapy with tempol reverses the imbalance of renal RAS components in obesity-related hypertension, which would be helpful to restore the renal function and lower blood pressure.