MECHANISM OF REDUCED GFR IN RABBITS WITH ISCHEMIC ACUTE RENAL FAILURE

Abstract

A reduction in glomerular filtration rate (GFR) is a primary characteristic of ischemic acute renal failure. The present study was undertaken to examine the roles of angiotensin II, tubuloglomerular-feedback (TGF) mechanism, and tubular obstruction for the GFR reduction in the postischemic kidney. Renal ischemia was induced by occlusion of the bilateral renal arteries for 60 min, and renal function was examined at 2 and 24 h after the onset of reflow. After the end of 2-h reflow, the GFR was not significantly changed, but the urine flow increased significantly. On the other hand, at the end of 24-h reflow, the GFR and urine flow decreased markedly along with increased filtration fraction. The renal blood flow significantly decreased at 24 h, but not 2 h, after reflow, which was accompanied by increased total renal vascular resistance. Furosemide infusion (1 mg/min/kg) after 24 h of reflow prevented the reduction in GFR and filtration fraction without no changes in renal blood flow and total renal vascular resistance. Pretreatment of enalapril and losartan did not prevent the reduction in GFR, indicating that angiotensin II was not involved. In morphological examinations, tubular obstruction was seen in the proximal and distal tubules of kidneys both at 2 and 24 h after the onset of reflow. In two rabbits subjected to 48 h of reflow, the tubular obstruction was not observed, despite GFR remained depressed. These results suggest that the late reduction in GFR in postischemic kidneys is not mediated by angiotensin II, but is mediated, at least in part, by the TGF mechanism. The tubular obstruction may be not prerequisite for the GFR reduction in rabbits.