1 Unilateral left renal artery occlusion for 1 h in a group of 8 untreated female Sprague-Dawley rats resulted in oliguric acute renal failure (ARF) persisting for more than 6 h after reflow, i.e. after reperfusion of the kidney by removal of the arterial clamp. In a second group of 8 rats with left unilateral ARF the effects of levemopamil (L), a calcium entry blocker with 5-hydroxytryptamine2 (5-HT2) receptor antagonistic properties, were studied. Rats received L as a continuous infusion (6 mg kg-' h-') from 1 h before ischaemia until 6 h after reflow. 2 Endogenous creatinine clearance, an estimate of glomerular filtration rate (GFR), of left ischaemic kidneys of untreated rats was almost completely abolished and urine flow was 0.05 + 0.02 and 0.03 + 0.01 ml h'-100 g' body weight (body wt.) at 2 and at 6 h of reflow, respectively. In contrast, left ischaemic kidneys of L-treated rats revealed significantly higher GFR (0.10 + 0.02 and 0.03+0.01 mlmin-' g kidney weight (k.wt.); P<0.01) and urine flow (0.51+0.05 and 0.15 +0.04 ml h-' 100 g' body wt.; P<0.05) at 2 and 6 h of reflow, respectively. 3 At 6 h of reflow, mitochondria from the cortex of left ischaemic kidneys of untreated rats showed significantly reduced ATP synthesis when compared to right intact kidneys (0.06 + 0.02 vs 0.26+0.02 ymol ATP mg-' protein min-' (P<0.01)). In contrast, in L-treated rats, ATP synthesis of left ischaemic kidneys was largely preserved (0.17+0.01 ymol ATP mg-' protein min-').4 Ischaemia of left kidneys resulted in a significant decrease in medullary Na-K-ATPase activity to 9.6+2.4 as compared to 20.4+3.7 ,umol Pi h-' mg-' protein in the intact right kidneys which was not prevented by L (9.4+2.4 ymol Pi h-' mg-' protein).5 In untreated rats the calcium content in cortical mitochondria from left ischaemic kidneys had risen 2 fold to 23.0+1.8 at 6 h of reflow as compared to 12.2 + 0.3 nmol mg-' protein in right intact kidneys (P<0.01). This rise in mitochondrial calcium was not significantly attenuated by treatment with L (19.9 + 1.7 nmol mg'-protein). 6 The results show that L transiently converted oliguria into non-oliguria during the early phase after reflow in ischaemic ARF, i.e. after reperfusion following 1 h of complete interruption of renal perfusion. The present data suggest indirectly that the 5-HT2-antagonistic properties of L rather than its calcium channel blocking action maintains GFR at low level and protects mitochondrial function early after reflow in this model of ischaemic ARF.
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