Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension.

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Abstract
Recent studies have indicated that acute inhibition of nitric oxide biosynthesis in the rat promotes arterial hypertension and renal vasoconstriction. We evaluated the renal and systemic effects of 4-6 weeks of nitric oxide blockade in Munich-Wistar rats receiving the nitric oxide inhibitor nitro-L-arginine orally. Age-matched untreated rats were used as controls. In an additional seven rats, nitric oxide blockade was carried out in conjunction with oral administration of the novel angiotensin II antagonist losartan potassium. Tail-cuff pressure rose progressively in nitro-L-arginine-treated rats, reaching 164 +/- 6 mm Hg at 4-6 weeks, compared with 108 +/- 3 mm Hg in controls. In rats concomitantly receiving losartan, tail-cuff pressure reached 125 +/- 6 mm Hg, still elevated compared with rats receiving losartan alone (98 +/- 3 mm Hg). Nitro-L-arginine-treated rats presented marked renal vasoconstriction and hypoperfusion, as well as a 30% fall in glomerular filtration rate and a 39% increase in filtrat...