NMR studies of the effect of Mg2+ on post-ischemic recovery of ATP and intracellular sodium in perfused kidney

[摘要] 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 P-31 and triple-quantum filtered (TQ) Na-23-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 Na-23 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 F-19-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.

[发布日期] 1995-12-12

[关键词] ischemia;magnesium;intracellular sodium;reperfusion;free calcium