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) inhibit s 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 chang es associated with this inhibition. Isolated kidneys (IK) were perfuse d at high pressure (175 mmHg) by a pump in series with intact Wistar a ssay rats in which blood pressure (BP), haemodynamics and renal functi on were studied. Nitric oxide (NO) synthesis was blocked by L-NNA (2.5 mg kg(-1)) in 13 experiments (175NO) while 14 control experiments (17 5C) were performed. IK was perfused at 90 mmHg in seven experiments (9 0C). 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 inf usion (20 mg kg(-1) min(-1)) BP declined also in 175NO. Effective rena l plasma flow (ERPF) and glomerular filtration rate (GFR) fell dramati cally after L-NNA in both the assay rat and in IK despite a high perfu sion pressure. The marked increase in filtration fraction (FF) after L -NNA suggests a dominating postglomerular vasoconstriction. The natriu retic response in IK to 175 mmHg was also markedly blunted by L-NNA. W e conclude that NO blockade inhibits the renomedullary depressor mecha nism probably by restricting renal blood flow, and also blunts the pre ssure induced natriuretic response as a result of a reduced sodium fil tration. Finally, the autoregulation of whole kidney blood flow seems to be more efficient although set at a higher level of vasoconstrictio n.