Effects of long-term losartan and L-arginine treatment on haemodynamics, glomerular filtration, and SOD activity in spontaneously hypertensive rats

Abstract

Recently, it has been reported that losartan, an angiotensin II receptor (ATR) antagonist, depresses the angiotensin II-induced production of superoxide radicals. Also, in spontaneously hypertensive rats (SHR) endothelial dysfunction is associated with decreased nitric oxide (NO) synthesis. In this study, we examined the effects of long-term ATR blockade and L-arginine supplementation on the haemodynamic parameters, glomerular filtration, and oxidative status in SHR. Adult male SHR were treated with losartan (10 mg/kg) and with the NO donor L-arginine (2 g/kg) for 4 weeks. The animals were divided into the following experimental groups: control (n = 7), L-arginine (n = 7), losartan (n = 7), and L-arginine + losartan (n = 7). Mean arterial pressure (MAP), regional blood flow, urea clearance, and activity of superoxide dismutase (SOD) were measured at the end of treatment. MAP was significantly reduced in the losartan group compared with the control group (133.3 +/- 7.3 vs. 161.5 +/- 14.5 mm Hg). Aortic blood flow was significantly higher and aortic vascular resistance was significantly lower in all treated groups than in the control. Urea clearance rose significantly in the L-arginine + losartan group compared with control (393.27 +/- 37.58 vs. 218.68 +/- 42.03 mu L center dot min(-1)center dot 100 g(-1)), as did the activity of SOD (1668.97 +/- 244.57 vs. 1083.18 +/- 169.96 U/g Hb). Our results suggest that the antihypertensive effect of losartan and L-arginine in SHR is not primarily mediated by increased SOD activity. Also, combined treatment with ATR blockade and L-arginine supplementation has a beneficial effect on renal function that is, at least in part, mediated by increased SOD activity in SHR.