EFFECTS OF ANTIHYPERTENSIVE THERAPY ON BLOOD-PRESSURE AND RENAL-FUNCTION IN RATS WITH HYPERTENSION DUE TO CHRONIC BLOCKADE OF NITRIC-OXIDE SYNTHESIS

Different antihypertensive treatment regimes were studied in rats during longterm inhibition of nitric oxide synthesis. Male Munich Wistar rats (weight 150-200 g) were put on oral L-nitro-arginine methyl ester (L-NAME, 50 mg/l drinking water) for 12 weeks. The control group (n = 16) received only tap water. Six weeks after starting L-NAME administration rats were divided into 7 groups (n = 13 in each group: group 1, no treatment; group 2, l-arginine 1 g/l drinking water; group 3, doxazosin 30 mg/kg/day; group 4, felodipine 25-30 mg/kg/day; group 5, losartan 40 mg/kg/day; group 6, metoprolol 300-350 mg/kg/day, and group 7, ramipril 1 mg/kg/day. Systolic blood pressure (sBP) was measured in the conscious rat 1, 6, and 12 weeks after study begin. After a treatment period of 6 weeks albuminuria, glomerular filtration rate (GFR) and renal plasma flow (RPF; inulin and p-aminohippuric acid clearance) were analyzed. All rats showed a significant increase in sBP under 6 weeks of L-NAME administration. Control rats remained normotensive during the whole study period. Rats receiving L-NAME without antihypertensive treatment showed a further increase in sBP after 12 weeks. Blood pressure was lowered in all treated animals, except in rats receiving I-arginine. Values for GFR were lowest in the placebo group, the E-arginine group and in rats receiving felodipine (p < 0.05 compared to the control group). RPF was lowest in the placebo group, the I-arginine group, the felodipine group and the ramipril group (p < 0.05 compared to the control group). Albuminuria was highest in the placebo group and the group receiving l-arginine, and was reduced by all drugs except for doxazosin and ramipril. These data demonstrate the efficacy of different antihypertensive drugs in blood pressure reduction and preservation of kidney function in a model of chronic hypertension with renal failure under chronic endothelium-derived relaxing factor blockade.