Effect of salt intake and inhibitor dose on arterial hypertension and renal injury induced by chronic nitric oxide blockade.
Long-term nitric oxide blockade by N omega -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.
Yamada
S S
SS
Department of Clinical Medicine, University of São Paulo Brazil School of Medicine, Brazil.
Sassaki
A L
AL
Fujihara
C K
CK
Malheiros
D M
DM
De Nucci
G
G
Zatz
R
R
D000419:Albuminuria; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009318:Natriuresis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation; D012083:Renin / Q000097:blood; D013997:Time Factors
D009569:Nitric Oxide; D001120:Arginine; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester