Arterial Pressure Response to the Antioxidant Tempol and ET B Receptor Blockade in Rats on a High-Salt Diet

Abstract
We hypothesized that increased superoxide contributes to mean arterial pressure (MAP) regulation in male Sprague-Dawley rats fed a high-salt diet and/or during endothelin (ET B ) receptor blockade. Four groups on either a normal- or a high-salt diet were studied for 1 week: (1) control; (2) tempol, a superoxide dismutase mimetic, in their drinking water (1 mmol/L); (3) A-192621, an ET B antagonist, in their food (10 mg/kg daily); or (4) both tempol and A-192621. Without ET B blockade, tempol had no effect on MAP (telemetry) in rats on the normal-salt diet but significantly reduced MAP in rats on the high-salt diet (100±3 vs 112±2 mm Hg, P 2 O 2 excretion was significantly higher in rats on a high-salt diet for the 7-day drug treatment compared with those on a normal-salt diet. Tempol further increased H 2 O 2 excretion in rats on a high-salt diet, an effect accelerated in A-192621–treated rats. These data suggest that blood pressure lowering by tempol in rats on a high-salt diet may be unrelated to reductions in superoxide and that renal H 2 O 2 may account for the limited ability of tempol to attenuate hypertension produced by ET B receptor blockade.