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Center for Anesthesiology Research, The Cleveland Clinic Foundation, Cleveland, Ohio
Submitted 20 February 2006 ; accepted in final form 19 May 2006
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 (105, 3 x 105, and 104 M) and thiopental (104 and 3 x 104 M) each attenuated levcromakalim relaxation in endothelium-intact (E+) rings, whereas propofol (3 x 105 and 104 M) and thiopental (3 x 104 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 (104 M) and thiopental (3 x 104 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.
Ca2+ influx; anesthetics
This article has been cited by other articles:
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X. Ding and P. A. Murray The Differential Effects of Intravenous Anesthetics on Myofilament Ca2+ Sensitivity in Pulmonary Venous Smooth Muscle Anesth. Analg., November 1, 2007; 105(5): 1278 - 1286. [Abstract] [Full Text] [PDF] |
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