Propofol causes vasodilation in vivo via TRPA1 ion channels: role of nitric oxide and BKCa channels.

Propofol causes vasodilation in vivo via TRPA1 ion channels: role of nitric oxide and BKCa channels.

Sinha Sayantani; Sinharoy Pritam; Bratz Ian N; Damron Derek S

PloS one

2015

1905-07

BACKGROUND: Transient receptor potential (TRP) ion channels of the A1 (TRPA1) and V1 (TRPV1) subtypes are key regulators of vasomotor tone. Propofol is an intravenous anesthetic known to cause vasorelaxation. Our objectives were to examine the extent to which TRPA1 and/or TRPV1 ion channels mediate propofol-induced depressor responses in vivo and to delineate the signaling pathway(s) involved. METHODS: Mice were subjected to surgery under 1.5-2.5% sevoflurane gas with supplemental oxygen. After a stable baseline in mean arterial pressure (MAP) was achieved propofol (2.5, 5.0, 10.0 mg/kg/min) was administered to assess the hemodynamic actions of the intravenous anesthetic. The effect of nitric oxide synthase (NOS) inhibition with L-NAME and/or calcium-gated K+ channel (BKCa) inhibition with Penetrim A (Pen A), alone and in combination, on propofol-induced decreases in mean arterial pressure were assessed in control C57Bl/6J, TRPA1-/-, TRPV1-/- and double-knockout mice (TRPAV-/-). RESULTS: Propofol decreased MAP in control mice and this effect was markedly attenuated in

Female; Male; Animals; Mice; Signal Transduction; TRPA1 Cation Channel; Arterial Pressure/drug effects; Vasodilator Agents/*pharmacology; Propofol/*pharmacology; Transient Receptor Potential Channels/genetics/*metabolism; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/*physiology; Nitric Oxide/*physiology; TRPV Cation Channels/genetics/metabolism; Inbred C57BL; Knockout; Drug Evaluation; Preclinical

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e0122189–e0122189

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