SODIUM EXCESS AGGRAVATES HYPERTENSION AND RENAL PARENCHYMAL INJURY INRATS WITH CHRONIC NO INHIBITION

Chronic nitric oxide (NO) inhibition promotes hypertension and ischemi c glomerular injury with only minor glomerulosclerosis (GS). We evalua ted the effect of superimposed salt overload, which has been shown to aggravate GS in other models. Fifteen days of treatment with the NO in hibitor 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 sligh tly exacerbated systemic and glomerular hypertension, promoted albumin uria, interstitial expansion, and glomerular ischemia, and paradoxical ly reversed hyporeninemia. The angiotensin II inhibitor losartan atten uated 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, intersti tial expansion, and ischemia and promoted massive albuminuria, GS, and creatinine retention. Losartan attenuated these effects. Sodium overl oad aggravates the renal and systemic consequences of chronic NO inhib ition by mechanisms that may include paradoxical activation of renin s ecretion. Interstitial expansion and glomerular ischemia, rather than GS, constitute the chief modalities of renal injury in this model.