TRPA1 and TRPV1 contribute to propofol-mediated antagonism of U46619-induced constriction in murine coronary arteries.

TRPA1 and TRPV1 contribute to propofol-mediated antagonism of U46619-induced constriction in murine coronary arteries.

Sinharoy Pritam; Bratz Ian N; Sinha Sayantani; Showalter Loral E; Andrei Spencer R; Damron Derek S

PloS one

2017

2017

BACKGROUND: Transient receptor potential (TRP) ion channels have emerged as key components contributing to vasoreactivity. Propofol, an anesthetic is associated with adverse side effects including hypotension and acute pain upon infusion. Our objective was to determine the extent to which TRPA1 and/or TRPV1 ion channels are involved in mediating propofol-induced vasorelaxation of mouse coronary arterioles in vitro and elucidate the potential cellular signal transduction pathway by which this occurs. METHODS: Hearts were excised from anesthetized mice and coronary arterioles were dissected from control C57Bl/6J, TRPA1-/-, TRPV1-/- and double-knockout mice (TRPAV-/-). Isolated microvessels were cannulated and secured in a temperature-controlled chamber and allowed to equilibrate for 1 hr. Vasoreactivity studies were performed in microvessels pre-constricted with U46619 to assess the dose-dependent relaxation effects of propofol on coronary microvascular tone. RESULTS: Propofol-induced relaxation was unaffected in vessels obtained from TRPV1-/- mice, markedly attenuated in pre-constricted vessels obtained from TRPA1-/- mice and abolished in vessels obtained from

Male; Animals; Mice; TRPV Cation Channels/genetics/*metabolism; TRPA1 Cation Channel; Endothelial Cells/drug effects/metabolism; Nitric Oxide Synthase Type III/metabolism; Vasodilator Agents/*pharmacology; Coronary Vessels/*drug effects/metabolism; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism; Microvessels/drug effects/metabolism; Propofol/*pharmacology; Transient Receptor Potential Channels/genetics/*metabolism; Vasoconstrictor Agents/antagonists & inhibitors/pharmacology; Vasodilation/drug effects/physiology; Cells; Cultured; Inbred C57BL; Knockout; 15-Hydroxy-11 alpha; 9 alpha-(epoxymethano)prosta-5; 13-dienoic Acid/*antagonists & inhibitors/pharmacology

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