NITRIC-OXIDE SYNTHASE BLOCKADE AND RENAL VASCULAR-RESPONSES TO NOREPINEPHRINE AND ENDOTHELIN-1 IN CONSCIOUS DOGS

The effects of inhibiting nitric oxide (NO) synthase with N-G-nitro-L- arginine (L-NNA) on renal vasoconstrictor responses to intrarenally ad ministered norepinephrine (NE) and endothelin-1 (ET-1) were studied in conscious dogs. NE was infused into the renal artery at 0.02, 0.05, 0 .1, and 0.2 mu g/kg/min (15 min at each rate), with the dogs (n = 5) p retreated with either L-NNA 10 mg/kg intravenously (i.v.) or vehicle ( 250 mM NaHCO3 solution at 2 ml/kg i.v.) NE produced dose-related decre ases in renal blood flow (RBF) and renal vascular conductance that wer e significantly greater after L-NNA pretreatment than after vehicle. E T-1 was infused intrarenally at 2.7 ng/kg/min for 45 min with the dogs (n = 5) pretreated with either L-NNA:10 mg/kg i.v. or vehicle. ET-1 c aused a progressive decrease in RBF and renal vascular conductance. In contrast to the results with NE, RBF and renal vascular conductance d ecreased significantly less in response to ET when the dogs were pretr eated with L-NNA as compared with pretreatment with vehicle. Therefore , blockade of NO synthase augmented NE-induced but not ET-induced rena l vasoconstriction. The results therefore suggest that NO may act to l essen the renal vascular effects of NE, but this effect does not appea r to be generalised to all vasoconstrictors.