Hepatic haemodynamic changes following inhibition of endothelium-derived relaxing and hyperpolarising factors in anaesthetised miniature pigs.
The influence of endothelium-dependent vasodilatation in regulating the hepatic circulation has been investigated by intraportal infusion of inhibitors of either endothelium-derived relaxing factor (NG-nitro-L-arginine-methyl-ester [L-NAME]) or of endothelium-derived hyperpolarising factor (ATP-dependent K(+)-channel inhibitor, glybenclamide) in barbiturate anaesthetised miniature pigs. Intraportal infusion of acetylcholine (5.5 micrograms kg-1 min-1 over 2 min) produced a selective 3-fold increase in hepatic artery and coeliac trunk blood flow, while mesenteric, portal, systemic, and pulmonary vascular beds remained unchanged. Intraportal L-NAME or glybenclamide did not reduce the hepatic artery and coeliac trunk flows but increased systemic and mesenteric vascular resistances. The acetylcholine-induced hepatic artery vasodilatation was partially blocked by 59%, 76% and 66% by L-NAME, at 30, 100, and 300 mg/kg respectively. Glybenclamide pretreatment up to 3 mg/kg did not modify acetylcholine-induced vasodilatation of the hepatic artery and coeliac trunk. Furthermore, prior cyclooxygenase inhibition did not alter the hepatic vascular response to acetylcholine. These results suggest that, in contrast to what is observed in large vessels, the hepatic vascular tree may not be entirely regulated by nitric oxide under basal conditions, but nitric oxide is released readily upon stimulation with acetylcholine, a response that is largely but incompletely blocked by L-NAME pretreatment. Neither basal vascular tone nor acetylcholine-induced vasorelaxation are mediated by the opening of glybenclamide-sensitive K+ channels in the hepatic circulation in pigs.
Treggiari-Venzi
M
M
Department of Anaesthesia, Pharmacology and Surgical Intensive Care, University Hospital of Geneva. treggmm@u.washington.edu
Schiffer
E R
ER
Romand
J A
JA
Licker
M
M
Morel
D R
DR
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D008099:Liver / Q000098:blood supply; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011169:Portal Vein; D026902:Potassium Channel Blockers; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013552:Swine; D013556:Swine, Miniature; D014655:Vascular Resistance / Q000187:drug effects
D026902:Potassium Channel Blockers; D009569:Nitric Oxide; D000109:Acetylcholine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester