The Potential Role of TRPA1 and TRPV1 in Propofol‐Induced Depressor Responses in vivo

TRPA1 and TRPV1 are channels thought to be involved in vasodilation and pain/inflammation pathways. The vasodilatory effect of propofol is thought to directly or indirectly be mediated by both channels. The main objective of this study was to determine the role of TRPV1/A1 in propofol‐induced vasodilation in‐vivo . Using a high‐fidelity microtip transducer catheter, changes in mean arterial blood pressure were recorded in C57Bl6 and TRPV1 (−/−) mice to propofol. Propofol (1–20 mg/kg) mediated a dose‐dependent depressor response in C57Bl6 mice which was significantly blunted by TRPA1 inhibition (HC‐030031, 60 mg/kg). Similar responses were observed in TRPV1 (−/−) mice. To investigate the role of nitric oxide in this response, L‐NAME pretreatment in both sets of mice demonstrated significantly attenuated propofol‐induced depressor responses, particularly in TRPV1 null mice. Calcium imaging demonstrated TRPA1‐induced increases in intracellular calcium in endothelial cells (ECs). Furthermore, immunocytochemistry demonstrated TRPA1 expression on human aortic ECs. Conclusions Our data clearly suggest a role for TRPA1 in propofol mediated vasodilation, which appears to involve endothelial TRPA1 activation and eNOS. A thorough knowledge of propofol mediated vasodilation via TRP channels will help to mitigate the potential harmful side effects of peri‐operative recovery in patients.