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(Hypertension. 1996;27:1165-1172.)
© 1996 American Heart Association, Inc.
Articles |
Effect of Salt Intake and Inhibitor Dose on Arterial Hypertension and Renal Injury Induced by Chronic Nitric Oxide Blockade
From the Renal Division, Department of Clinical Medicine, University of São Paulo (Brazil) School of Medicine, and Department of Pharmacology, State University of Campinas (Brazil) School of Medicine.
Correspondence to Roberto Zatz, MD, PhD, Laboratório de Fisiopatologia Renal, Av Dr Arnaldo, 455, 3-s/67, 01246-903 São Paulo SP, Brazil.
Abstract Long-term nitric oxide blockade by
N
-nitro-L-arginine methyl ester
(L-NAME) leads to severe and progressive hypertension. The role of salt
intake in this model is unclear. To verify whether salt dependence in
this model is related to the extent of nitric oxide inhibition, we gave
adult male Munich-Wistar rats a low salt, standard salt, or high 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
untreated controls. In rats treated with the higher dose, the line was
shifted 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 vasoconstriction that was aggravated by salt overload.
Low-dose L-NAME treatment induced hypertension only when associated
with sodium overload. In rats receiving high-dose L-NAME,
hypertension was aggravated by sodium excess but was not ameliorated by
sodium restriction. Long-term (6 weeks) L-NAME treatment was
associated with progressive hypertension, which was aggravated by salt
overload, and with the development of albuminuria, focal
glomerular collapse,
glomerulosclerosis, and renal
interstitial expansion. These abnormalities were worsened
by salt overload and largely prevented by salt restriction. In the
model of chronic nitric oxide blockade, salt dependence is a function
of the inhibitor dose, and renal injury varies directly
with the level of salt intake.
Key Words: nitric oxide • kidney • salt • pressure natriuresis
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