Effects of chronic increased salt intake on nitric oxide synthesis inhibition-induced hypertension

Experimental evidence suggests that endogenous nitric oxide plays an important role in the homeostatic response to an increase in sodium intake. In the present study we evaluated the influence of a high sodium intake (1% NaCl as drinking water) on arterial hypertension induced by long-term (6-7 weeks) inhibition of nitric oxide synthesis [NG-nitro-L-arginine methyl ester (L-NAME), 75 mg/100 ml in the drinking fluid] in rats.

Treatment with L-NAME induced progressive elevations in tail-cuff systolic blood pressure, but there were no differences between rats drinking tap water and rats drinking 1% NaCl. Direct measurement of blood pressure at the end of the treatment confirmed the hypertension and the lack of differences between the two groups treated with L-NAME. Metabolic studies performed at the end of L-NAME treatment showed a reduced glomerular filtration rate and elevated urinary excretion of immunoreactive endothelin in the two hypertensive groups treated with L-NAME. Drinking intake, diuresis and natriuresis were significantly higher only in the L-NAME group drinking 1% NaCl. Both groups treated with L-NAME showed an accelerated and increased diuretic and natriuretic response to an isotonic 0.9% NaCl load (2.5 ml/100 g body weight, intraperitoneally). At the end of the study ventricular hypertrophy was observed in both L-NAME groups.

The present results indicate that the time-dependent elevation in blood pressure produced by long-term inhibition of nitric oxide production is not affected by an increased sodium intake. However, salt supplementation induced the development of a polyuria and polydipsia syndrome in rats treated with L-NAME. The elevated excretion of endothelin in both groups treated with L-NAME suggests the possible participation of endothelin in the development of L-NAME hypertension.