Propofol regulation of vascular reactivity is mediated via TRP channels

Abstract

Transient receptor potential channels, TRPA1 and TRPV1 are known to play a major role in pain and inflammatory pathways. Recent evidences have shown that general anesthetics can either directly or indirectly sensitize these channels. Similarly studies have also implicated cross‐talk between these channels which plays an immense role in regulating these channels. Propofol, an intravenous anesthetic, causes hypotension when administered to patients during surgery. Our main objective was to determine the role of these channels in the regulation of vascular reactivity while further demonstrating Propofol mediates vasodilation through TRPA1/TRPV1 signaling. Using high‐fidelity microtip transducer catheter, changes in mean arterial pressure were recorded in C57BL6 and TRPA1(−/−) mice. Propofol induced a dose‐dependent depressor response which was blunted in TRPA1(−/−) mice and was further attenuated in TRPA1(−/−) mice in the presence of a specific TRPV1 antagonist SB366791. Isometric‐tension studies in endothelium intact and denuded aortic rings from TRPA1(−/−)mice in presence/absence of SB366791 illustrated a role for TRPA1/TRPV1. Furthermore propofol elicited robust relaxation in isolated coronary microvessel from controls which was blunted in the presence of SB366791 and in vessels from TRPA1(−/−)mice. In conclusion, Propofol mediated regulation of vascular reactivity occurs in part via combined TRPA1/TRPV1 mediated signaling.