Nitric oxide mediates hepatic arterial vascular escape from norepinephrine-induced constriction.
The involvement of nitric oxide (NO) in the vascular escape from norepinephrine (NE)-induced vasoconstriction was investigated in the hepatic arterial vasculature of anesthetized cats. The hepatic artery was perfused by free blood flow or pump-controlled constant-flow, and NE (0.15 and 0.3 microg x kg(-1) x min(-1), respectively) was infused through the portal vein. In the free-flow perfusion model, the NE-induced hepatic vasoconstriction recovered from the maximum point of the constriction, resulting in 36.6 +/- 5. 9% vascular escape. Blockade of NO formation with N(omega)-nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg ipv) potentiated NE-induced maximum vasoconstriction, and the potentiation was reversed by L-arginine (75 mg/kg ipv). Furthermore, NE-induced vasoconstriction became more stable after L-NAME, resulting in an inhibition of vascular escape (7.5 +/- 3.3%), and the inhibition was reversed by L-arginine (23.0 +/- 6.4%). Similar potentiation of NE-induced vasoconstriction and inhibition of hepatic vascular escape by L-NAME (40.4 +/- 4.3% control vs. 10.2 +/- 3.7% post-L-NAME escape) and the reversal by L-arginine were also observed in the constant-flow perfusion model. The data suggest that NO is the major endogenous mediator involved in the hepatic vascular escape from NE-induced vasoconstriction.
Ming
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3.
Han
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Lautt
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D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure; D002415:Cats; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006499:Hepatic Artery / Q000502:physiology*; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine