RENAL AND HEMODYNAMIC-EFFECTS OF NITRIC-OXIDE BLOCKADE IN A WISTAR ASSAY RAT DURING HIGH-PRESSURE CROSS-CIRCULATION OF AN ISOLATED DENERVATED KIDNEY

Blockade of NO synthesis with N-omega-nitro-L-arginine (L-NNA) inhibits the vasodepressor response seen in intact Wistar assay rats in which isolated kidneys perfused via an extracorporeal circuit are perfused at high pressure. This study explores the renal and haemodynamic changes associated with this inhibition. Isolated kidneys (IK) were perfused at high pressure (175 mmHg) by a pump in series with intact Wistar assay rats in which blood pressure (BP), haemodynamics and renal function were studied. Nitric oxide (NO) synthesis was blocked by L-NNA (2.5 mg kg(-1)) in 13 experiments (175NO) while 14 control experiments (175C) were performed. IK was perfused at 90 mmHg in seven experiments (90C). The BP drop in the 175C assay rat was blocked by L-NNA in 175NO (P < 0.01). However, when the blockade was reversed with L-arginine infusion (20 mg kg(-1) min(-1)) BP declined also in 175NO. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) fell dramatically after L-NNA in both the assay rat and in IK despite a high perfusion pressure. The marked increase in filtration fraction (FF) after L-NNA suggests a dominating postglomerular vasoconstriction. The natriuretic response in IK to 175 mmHg was also markedly blunted by L-NNA. We conclude that NO blockade inhibits the renomedullary depressor mechanism probably by restricting renal blood flow, and also blunts the pressure induced natriuretic response as a result of a reduced sodium filtration. Finally, the autoregulation of whole kidney blood flow seems to be more efficient although set at a higher level of vasoconstriction.