Propofol and thiopental attenuate adenosine triphosphate-sensitive potassium channel relaxation in pulmonary veins

Abstract

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.

Propofol and Aminophylline Antagonize Each Other During the Mobilization of Intracellular Calcium in Human Umbilical Vein Endothelial Cells

“…In endothelial cells, the activation of adenosine-triphosphate-sensitive potassium channels (K + ATP channels) is dependent upon L-type, voltage-gated calcium channels, and causes an increase in K + efflux, membrane hyperpolarization and calcium influx (15). Propofol attenuates the effect of K + ATP channels by inhibiting the nitric oxide pathway (16). The mobilization of calcium from intracellular stores is related to the hydrolysis of inositol-4,5-biphosphate (PIP2) to diacylglycerol and IP3 (17).…”

“…First, propofol blocks the voltage-gated influx of extracellular Ca 2+ by acting as a calcium channel blocker (6), but aminophylline induced an influx of Ca 2+ by activating calcium channels (23, 24). Second, propofol reduces the production of IP3 and calcium release from intracellular stores (16, 17), but aminophylline induced Ca 2+ release from intracellular stores, occurs via increased production of IP3 through G-protein-mediated activation (21, 25). …”

The effects of propofol on vascular function in mesenteric arteries of the aging rat

“…However, there are reports where relaxation does not occur, and these differences may be species and vascular bed specific. For example, it has been shown to enhance constriction/inhibit relaxation in the rabbit mesenteric artery (15,36) as well as the pulmonary arteries and veins of the dog (14,24,30). Additional evidence for the vascular bed-specific effects of propofol include studies documenting varying effects of propofol on modulating the responses in different blood vessels in the same animal (11,15).…”