EFFECT OF CALCIUM-CHANNEL BLOCKER ON NA-K ATPASE DURING ACUTE ISCHEMIC RENAL-FAILURE

초록

. The derangement of cellular calcium homeostasis has been well-known to play an important role in the pathophysiology of acute ischemic renal failure. With ischemic injury, Na-K ATPase which is normally located exclusively in the basolateral membrane moves to the luminal membrane. We investigated the effect of calcium channel blocker on the changes of renal tubular Na-K ATPase during acute ischemic renal failure by renal artery occlusion. The experimental animals were perfused with 2% paraformaldehyde and 0.25% glutaraldehyde as fixatives. All renal tissues were cryocut with 20 im thickness, and incubated in the presence of a lead ammonium citrate acetate complex, and observed by light microscope and electron microscope. The results were as follows: (I) Serum creatinine level was 0.44 0.22 mg/dl in the control group, 0.75 0.19 mg/dl in the ischemic group after 1 hour reperfusion, and 2.94 0.99 mg/dl in the ischemic group after 24 hour reperfusion. The mean serum creatinine level was statistically significant between the control and the post-ischemic 24 hour reperfusion groups (P < 0.05). (2) The fine granular reaction product of Na-K ATPase was present predominantly at the corticomedullary junction in the basolateral area of the thick ascending limb of Henle's loop, distal convoluted tubule and proximal convoluted tubule in the control group. (3) In the ischemic group without nifedipine pretreatment, the reaction products were decreased and focally located in the luminal membrane after 1 hour reperfusion. There were no significant differences between the 1 hour and 24 hour reperfusion groups. (4) In the nifedipine pretreatment ischemic group, reaction products were located in the basolateral membrane and the reactivity was decreased less than the ischemic group without nifedipme pretreatment group. From the above findings, Na-K ATPase was translocated to the luminal membrane from basolateral membrane in acute ischemic renal failure. This translocation of Na-K ATPase was related to loss of epithelial cell polarity secondary to loosening the tight junction in acute ischemic renal failure. The loss of epithelial cell polarity could be inhibited by administration of calcium channel blockers. During the early reperfusion phase in the ischemic model pretreated with calcium channel blocker, Na-K ATPase reactivity was as strong as the control group, so we suggested that calcium channel blockers could affect the progression of acute ischemic renal failure.