EFFECT OF SALT INTAKE AND INHIBITOR DOSE ON ARTERIAL-HYPERTENSION ANDRENAL INJURY-INDUCED BY CHRONIC NITRIC-OXIDE BLOCKADE

Long-term nitric oxide blockade by N-omega-nitro-L-arginine methyl est er (L-NAME) leads to severe and progressive hypertension. The role of salt intake in this model is unclear. To verify whether salt dependenc e in this model is related to the extent of nitric oxide inhibition, w e gave adult male Munich-Wistar rats a low salt, standard salt, or hig h salt diet and oral L-NAME treatment at either 3 or 25 mg/kg per day. At 10 to 15 days of treatment, the slope of the pressure natriuresis line was decreased in rats receiving low-dose L-NAME compared with unt reated controls. In rats treated with the higher dose, the line was sh ifted to the right but remained parallel to that obtained in untreated controls. Renal vascular resistance was moderately increased in rats receiving low-dose L-NAME, whereas high-dose L-NAME induced a marked v asoconstriction that was aggravated by salt overload. Low-dose L-NAME treatment induced hypertension only when associated with sodium overlo ad. In rats receiving high-dose L-NAME, hypertension was aggravated by sodium excess but was not ameliorated by sodium restriction. Long-ter m (6 weeks) L-NAME treatment was associated with progressive hypertens ion, which was aggravated by salt overload, and with the development o f albuminuria, focal glomerular collapse, glomerulosclerosis, and rena l interstitial expansion. These abnormalities were worsened by salt ov erload and largely prevented by salt restriction. In the model of chro nic nitric oxide blockade, salt dependence is a function of the inhibi tor dose, and renal injury varies directly with the level of salt inta ke.