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 NG-nitro-L-arginine (L-NNA) on renal vasoconstrictor responses to intrarenally administered 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 micrograms/kg/min (15 min at each rate), with the dogs (n = 5) pretreated 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 decreases in renal blood flow (RBF) and renal vascular conductance that were significantly greater after L-NNA pretreatment than after vehicle. ET-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 caused a progressive decrease in RBF and renal vascular conductance. In contrast to the results with NE, RBF and renal vascular conductance decreased significantly less in response to ET when the dogs were pretreated with L-NNA as compared with pretreatment with vehicle. Therefore, blockade of NO synthase augmented NE-induced but not ET-induced renal vasoconstriction. The results therefore suggest that NO may act to lessen the renal vascular effects of NE, but this effect does not appear to be generalised to all vasoconstrictors.
Fitzgerald
S M
SM
Emily E. E. Stewart Renal Laboratory, Baker Medical Research Institute, Melbourne, Australia.
Evans
R G
RG
Christy
I J
IJ
Anderson
W P
WP
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D016232:Endothelins; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine