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Am J Physiol Regul Integr Comp Physiol 281: R730-R737, 2001;
0363-6119/01 $5.00
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Vol. 281, Issue 3, R730-R737, September 2001

N-acetyl-L-cysteine improves renal medullary hypoperfusion in acute renal failure

Erica López Conesa1, Fernando Valero2, José Carlos Nadal2, Francisco J. Fenoy2, Bernardo López2, Begoña Arregui2, and Miguel García Salom2

1 Iffa-Credo, Domaine des Oncins, BP 0109, 69592 L'Arbresle Cedex, France; and 2 Departamento de Fisiología y Farmacología, Facultad de Medicina, 30100 Murcia, Spain

This study evaluated the effects of N-acetyl-L-cysteine (NAC), a free radical scavenger, and Nomega -nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthesis inhibitor, on the changes in renal function, intrarenal blood flow distribution (laser-Doppler flowmetry), and plasma peroxynitrite levels during the acute renal failure (ARF) produced by inferior vena cava occlusion (IVCO; 45 min) in anesthetized rats. Renal blood flow fell on reperfusion (whole kidney by -45.7%; cortex -58.7%, outer medulla -62.8%, and papilla -47.7%); glomerular filtration rate (GRF) also decreased (-68.6%), whereas fractional sodium excretion (FENa%) and peroxynitrite and NO<UP><SUB>2</SUB><SUP>−</SUP></UP>/NO<UP><SUB>3</SUB><SUP>−</SUP></UP> plasma levels increased (189.5, 46.5, and 390%, respectively) after ischemia. Pretreatment with L-NAME (10 µg · kg-1 · min-1) aggravated the fall in renal blood flow seen during reperfusion (-60%). Pretreatment with NAC (150 mg/kg bolus + 715 µg · kg-1 · min-1 iv) partially prevented those changes in renal function (GFR only fell by -29.2%, and FENa% increased 119.4%) and laser-Doppler blood flow, especially in the outer medulla, where blood flow recovered to near control levels during reperfusion. These beneficial effects seen in rats given NAC seem to be dependent on the presence of NO, because they were abolished in rats pretreated with L-NAME. Also, the antioxidant effects of NAC prevented the increase in plasma peroxynitrite after ischemia. In conclusion, NAC ameliorates the renal failure and the outer medullary vasoconstriction induced by ICVO, effects that seem to be dependent on the presence of NO and the scavenging of peroxynitrite.

inferior vena cava occlusion; free radical scavengers; peroxynitrite; nitric oxide; plasma nitrite/nitrate; renal function; laser-Doppler flowmetry


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