Propofol and thiopental attenuate adenosine triphosphate-sensitive potassium channel relaxation in pulmonary veins.
Pulmonary veins (PV) make a significant contribution to total pulmonary vascular resistance. We investigated the cellular mechanisms by which the intravenous anesthetics propofol and thiopental alter adenosine triphosphate-sensitive potassium (KATP+) channel relaxation in canine PV. The effects of KATP+ channel inhibition (glybenclamide), cyclooxygenase inhibition (indomethacin), nitric oxide synthase inhibition (L-NAME), and L-type voltage-gated Ca2+ channel inhibition (nifedipine) on vasorelaxation responses to levcromakalim (KATP+ channel activator) alone and in combination with the anesthetics were assessed. The maximal relaxation response to levcromakalim was attenuated by removing the endothelium and by L-NAME, but not by indomethacin. Propofol (10(-5), 3x10(-5), and 10(-4) M) and thiopental (10(-4) and 3x10(-4) M) each attenuated levcromakalim relaxation in endothelium-intact (E+) rings, whereas propofol (3x10(-5) and 10(-4) M) and thiopental (3x10(-4) M) attenuated levcromakalim relaxation in endothelium-denuded (E-) rings. In E+ rings, the anesthesia-induced attenuation of levcromakalim relaxation was decreased after pretreatment with L-NAME but not with indomethacin. In E-strips, propofol (10(-4) M) and thiopental (3x10(-4) M) inhibited decreases in tension and intracellular Ca2+ concentration ([Ca2+]i) in response to levcromakalim, and these changes were abolished by nifedipine. These findings indicate that propofol and thiopental attenuate the endothelium-dependent component of KATP+ channel-induced PV vasorelaxation via an inhibitory effect on the nitric oxide pathway. Both anesthetics also attenuate the PV smooth muscle component of KATP+ channel-induced relaxation by reducing the levcromakalim-induced decrease in [Ca2+]i via an inhibitory effect on L-type voltage-gated Ca2+ channels.
Roh
Woon-Seok
WS
Center for Anesthesiology Research, NE63, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.
Ding
Xueqin
X
Murray
Paul A
PA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000008:administration & dosage / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D019806:Cromakalim / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015221:Potassium Channels / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D011667:Pulmonary Veins / Q000378:metabolism / Q000502:physiology*; D013874:Thiopental / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D013874:Thiopental; D015742:Propofol