Dynamic Changes in Renal Ca2+ATPase Activity after Acute Intrauterine Ischemia in Fetal Rats

Abstract:

OBJECTIVE: To study the dynamic changes in renal Ca2+ ATPase after acute intrauterine ischemia in fetal rats,and to explore the underlying mechanism of intracelluar Ca2+ overload secondary to perinatal asphyxia.METHODS: A rat model of acute intrauterine ischemia was developed using different degrees of clamping of the vesseles supplying blood to the uterus. A graded reperfusion model was made by reperfusing the uterine vessels for different lengths of time after clamping. The activity of Ca2+ATPase in cell membranes and mitochondrial fractions in fetal rat kidneys was assayed biochemically.RESULTS: Ca2+ATPase activity in cell membranes and mitochondria in the shamoperated group was (7.476±0.353) and (3.470±0.270) μmol.Pi/mgprot.h respectively. Activities in both fractions decreased after 15 minutes of ischemia ［(6.411±0.210) and (2.886±0.245) μmol.Pi/mgprot.h respectively; P<0.01］ and continued to decrease after 45 minutes ［(5.772±0.177) and (2.500±0.282) μmol.Pi/mgprot.h respectively; P<0.05］. During the reperfusion stage (after 15 minutes of ischemia), activities continued to decrease reaching a nadir after 8 hours ［(5.513±0.197) and (2.411±0.197) μmol.Pi/mgprot.h respectively］. There was significant difference between the 8hour reperfusion group and the 15-minute ischemia group (P<0.01). After 15 h of reperfusion enzyme activity levels began to increase. By 24 hours, the activity of Ca2+ATPase in cell membranes had increased to normal levels, but the actvity in mitochondria was still low compared with the 15-minute ischemia group ［(3.234±0.143) and (2.886±0.245) μmol.Pi/mgprot.h respectively; P<0.05］. CONCLUSIONS: Ca2+ATPase activity decreases in the fetal kidney after acute intrauterine ischemia. Dynamic changes in Ca2+ATPase activity may explain the intracellular Ca2+ overload leading to hypoxic ischemic renal injury.