Supplementation with a low dose of l‐arginine reduces blood pressure and endothelin‐1 production in hypertensive uraemic rats

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Abstract
Background. We documented recently that increased endothelin‐1 (ET‐1) production in blood vessels and glomeruli of uraemic rats plays a crucial role in the development of hypertension and the progression of chronic renal failure. Normally, biological effects and local production of ET‐1 are attenuated by the immediate release of nitric oxide (NO). Increasing evidence suggest, however, that NO release is impaired in chronic renal failure. We investigated whether supplementation with l‐arginine, the natural precursor of NO, improves NO synthesis in uraemic rats with reduced renal mass and modulates vascular and renal ET‐1 production as well as blood pressure and renal failure progression. Methods. One week after surgical renal mass reduction, the uraemic and sham‐operated animals received either no treatment or 0.1% l‐arginine in drinking water for 5 weeks. In another series of experiments, uraemic rats received 1% l‐arginine for 5 weeks. Immunoreactive‐ET‐1 (ir‐ET‐1) levels in plasma, urine, and vascular and renal tissue preparations was measured by radioimmunoassay after sample extraction and purification. Results. Before treatment, systolic blood pressure was significantly elevated in uraemic animals compared to sham‐operated controls (156±7 vs 111±3 mmHg, respectively; PPPPP2/NO3 levels in l‐arginine‐treated animals (PPPConclusions. These results indicate that improvement of NO release with a low dose but not with a high dose of l‐arginine significantly attenuates the development of hypertension and the progression of renal insufficiency in rats with reduced renal mass. These protective effects may be mediated in part by the reduction of vascular and renal ET‐1 production.