N-acetyl-L-cysteine improves renal medullary hypoperfusion in acute renal failure.
This study evaluated the effects of N-acetyl-L-cysteine (NAC), a free radical scavenger, and N(omega)-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 (FE(Na%)) and peroxynitrite and NO/NO plasma levels increased (189.5, 46.5, and 390%, respectively) after ischemia. Pretreatment with L-NAME (10 microg. kg(-1). min(-1)) aggravated the fall in renal blood flow seen during reperfusion (-60%). Pretreatment with NAC (150 mg/kg bolus + 715 microg. kg(-1). min(-1) iv) partially prevented those changes in renal function (GFR only fell by -29.2%, and FE(Na%) 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.
Conesa
E L
EL
Iffa-Credo, Domaine des Oncins, BP 0109, 69592 L'Arbresle Cedex, France.
Valero
F
F
Nadal
J C
JC
Fenoy
F J
FJ
López
B
B
Arregui
B
B
Salom
M G
MG
D000111:Acetylcysteine / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007679:Kidney Medulla / Q000098:blood supply* / Q000187:drug effects* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D015424:Reperfusion; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology; D014682:Vena Cava, Inferior / Q000502:physiology
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D009566:Nitrates; D009573:Nitrites; C039642:peroxynitric acid; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine