NMR studies of the effect of Mg 2 on post-ischemic recovery of ATP and intracellular sodium in perfused kidney

Abstract

Ischemia is often implicated as a cause of acute renal failure. We have investigated the effect of various concentrations of extracellular Mg 2+ 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 Mg 2+ 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 Mg 2+ throughout (88 ± 5% recovery of [ATP] and 158 ± 8% accumulation of [P i]). Kidneys exposed to 0.3 MM Mg 2+ during the pre-ischemic and ischemic periods but to 1.2 mM Mg 2+ during reperfusion also showed better recovery of ATP (83 ± 6%) and lower accumulation of P i (143 ± 8%) compared to kidneys exposed to low Mg 2+ (0.3 mM) throughout the experiment. Measurements of the 23Na TQ signal following ischemia-reperfusion revealed that kidneys exposed to 1.2 mM Mg 2+ exhibited significantly improved maintenance of low intracellular Na + as compared to those exposed to 0.3 MM Mg 2+ ([Na +] i = 107 ± 7% in 1.2 mM Mg 2+ vs. 152 ± 3% in 0.3 mM Mg 2+. No significant difference was found in the pre-ischemic basal intracellular free Ca 2+ level (as measured by 19F-NMR in combination with 5 FBAPTA) between kidneys perfused with 1.2 mM and 0.3 MM Mg 2+, and comparable depletion of ATP occurred during ischemia under both experimental conditions. These data indicate that increased extracellular Mg 2+ 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.