NMR studies of the effect of Mg2+ on post-ischemic recovery of ATP and intracellular sodium in perfused kidney.
Ischemia is often implicated as a cause of acute renal failure. We have investigated the effect of various concentrations of extracellular Mg2+ on the post-ischemic recovery of ATP and low intracellular Na+ in the isolated perfused rat kidney using 31P and triple-quantum filtered (TQ) 23Na-NMR spectroscopy. Following a 1 h period of stopped flow ischemia, the kidneys exposed to 0.3 mM Mg2+ throughout the experiment exhibited a significantly (p < 0.05) decreased post-ischemic fractional recovery of ATP (56 +/- 7%) as well as a significantly (p < 0.05) increased accumulation of P(i) (250 +/- 30%) as compared to kidneys exposed to 1.2 mM Mg2+ throughout (88 +/- 5% recovery of [ATP] and 158 +/- 8% accumulation of [P(i)]). Kidneys exposed to 0.3 mM Mg2+ during the pre-ischemic and ischemic periods but to 1.2 mM Mg2+ during reperfusion also showed better recovery of ATP (83 +/- 6%) and lower accumulation of P(i) (143 +/- 8%) compared to kidneys exposed to low Mg2+ (0.3 mM) throughout the experiment. Measurements of the 23Na TQ signal following ischemia-reperfusion revealed that kidneys exposed to 1.2 mM Mg2+ exhibited significantly improved maintenance of low intracellular Na+ as compared to those exposed to 0.3 mM Mg2+ ([Na+]i = 107 +/- 7% in 1.2 mM Mg2+ vs. 152 +/- 3% in 0.3 mM Mg2+). No significant difference was found in the pre-ischemic basal intracellular free Ca2+ level (as measured by 19F-NMR in combination with 5 FBAPTA) between kidneys perfused with 1.2 mM and 0.3 mM Mg2+, and comparable depletion of ATP occurred during ischemia under both experimental conditions. These data indicate that increased extracellular Mg2+ has a protective effect against post-ischemic damage, probably related to its role in resynthesis of ATP during post-ischemic reperfusion. Our results would imply a greater vulnerability of the kidney to ischemic damage in hypomagnesemic clinical conditions such as alcoholism and diabetes.
Department of Physiology and Biophysics, Albert Einstein College of Medicine, Yeshiva University, New York, NY 10461, USA.
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Dowd
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Gupta
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D005110:Extracellular Space; D007424:Intracellular Fluid / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism*; D008274:Magnesium / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D012964:Sodium / Q000378:metabolism*
D000255:Adenosine Triphosphate; D012964:Sodium; D008274:Magnesium