Sodium excess aggravates hypertension and renal parenchymal injury in rats with chronic NO inhibition.
Chronic nitric oxide (NO) inhibition promotes hypertension and ischemic glomerular injury with only minor glomerulosclerosis (GS). We evaluated the effect of superimposed salt overload, which has been shown to aggravate GS in other models. Fifteen days of treatment with the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) promoted marked arterial and glomerular hypertension, hyporeninemia, and slight renal interstitial expansion, but no glomerular injury. Salt overload slightly exacerbated systemic and glomerular hypertension, promoted albuminuria, interstitial expansion, and glomerular ischemia, and paradoxically reversed hyporeninemia. The angiotensin II inhibitor losartan attenuated glomerular and systemic hypertension and prevented renal injury in these rats. Thirty days of treatment with L-NAME resulted in marked hypertension, hyperreninemia, interstitial expansion, and glomerular ischemia. Concomitant salt overload exacerbated hypertension, interstitial expansion, and ischemia and promoted massive albuminuria, GS, and creatinine retention. Losartan attenuated these effects. Sodium overload aggravates the renal and systemic consequences of chronic NO inhibition by mechanisms that may include paradoxical activation of renin secretion. Interstitial expansion and glomerular ischemia, rather than GS, constitute the chief modalities of renal injury in this model.
Fujihara
C K
CK
Department of Clinical Medicine, University of São Paulo School of Medicine, Brazil.
Michellazzo
S M
SM
de Nucci
G
G
Zatz
R
R
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D007511:Ischemia; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009336:Necrosis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012982:Sodium, Dietary
D012982:Sodium, Dietary; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester