Magnesium is a potent
vasodilator whose effects have not been evaluated in renal
ischemia. The
antioxidant properties of
N-acetylcysteine (NAC) partially protect animals from ischemic/
reperfusion injury. This study was designed to evaluate
magnesium supplementation, alone or combined with NAC, on ischemic
acute renal failure. Rats were maintained on normal diets, supplemented or not with MgCl(2).6H(2)O (1% in
drinking water) for 23 d, and some rats received NAC (440 mg/kg body wt) on days 20 to 23. On day 21,
ischemia was induced by clamping both renal arteries for 30 min. Five groups were studied: Normal,
ischemia, ischemia+magnesium, ischemia+NAC, and
ischemia+
magnesium+NAC. GFR (
inulin clearance), renal blood flow (RBF), FEH(2)O, and FENa were determined. Serum
magnesium was decreased in
ischemia-only rats.
Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. However, NAC completely restored the tubular damage induced by
ischemia/reperfusion. Semiquantitative immunoblotting showed that NAC prevented the decreased expression of Na-K-2Cl
co-transporter and
aquaporin 2 after renal
ischemia/reperfusion. Untreated rats with
acute renal failure demonstrated markedly decreased
endothelial nitric oxide synthase expression. Significantly, treatment with NAC,
magnesium, or both completely inhibited downregulation of
endothelial nitric oxide synthase. The tubular
necrosis scores were lower in rats that were treated with NAC alone or with the
magnesium-NAC combination.
Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. The NAC protected tubules from
ischemia, decreased infiltrating macrophages/lymphocytes, and had a mild protective effect on GFR. In ischemic/
reperfusion injury, renal function benefits more from the
magnesium-NAC combination than from
magnesium alone.