INFLUENCE OF KETANSERIN ON EXPERIMENTAL LOSS OF RENAL BLOOD-FLOW AUTOREGULATION

Serotonin is important for effective renal blood flow (RBF) autoregula tion in the normal rat and at two or seven days of reperfusion followi ng renal ischemia. It has been suggested that after these reperfusion periods and during renal perfusion pressure (RPP) lowering, the vasodi latory autoregulation mechanism is not damaged but overwhelmed by incr eased 5-HT2-mediated vasoconstriction, resulting: in complete loss of autoregulation. This study analyzes the influence of the 5-HT2- antago nist ketanserin on RBF autoregulation after two hours or one day of re nal reperfusion following ischemia and in a model of cyclosporine (20 mg/kg/day for 10 days)-induced nephrotoxicity. Autoregulation was lost both after brief reperfusion periods and after cyclosporine. Similar to the two or seven days of reperfusion experiments, ketanserin in the cyclosporine model led to reappearance of autoregulation down to RPP 95 mm Hg. Despite an increased response to intrarenal serotonin after two hours of reperfusion, autoregulation was not restored by ketanseri n, ht one day of reperfusion and with ketanserin. autoregulation was p resent down to 105 mm Hg. Thus, during the early reflow period, other factors (of decreasing importance) most likely add to autoregulation l oss.