Sinharoy Pritam, Bratz Ian N, Sinha Sayantani, Showalter Loral E, Andrei Spencer R, Damron Derek S
Department of Anesthesia, Perioperative and Pain Medicine, Stanford School of Medicine, Stanford, California, United States of America.
Department of Integrative Medical Sciences, Northeast Ohio Medical College, Rootstown, Ohio, United States of America.
PLoS One. 2017 Jun 23;12(6):e0180106. doi: 10.1371/journal.pone.0180106. eCollection 2017.
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.
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.
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 TRPAV-/- mice. Furthermore, NOS inhibition with L-NAME or endothelium denuding abolished the proporfol-induced depressor response in pre-constricted vessels obtained from all mice. In the absence of L-NAME, BKCa inhibition with penitrem A markedly attenuated propofol-mediated relaxation in vessels obtained from wild-type mice and to a lesser extent in vessels obtained from TRPV1-/-, mice with no effect in vessels obtained from TRPA1-/- or TRPAV-/- mice.
TRPA1 and TRPV1 appear to contribute to the propofol-mediated antagonism of U46619-induced constriction in murine coronary microvessels that involves activation of NOS and BKCa.
瞬时受体电位（TRP）离子通道已成为影响血管反应性的关键组成部分。丙泊酚是一种麻醉剂，与包括低血压和输注时急性疼痛在内的不良副作用相关。我们的目的是确定TRPA1和/或TRPV1离子通道在体外介导丙泊酚诱导的小鼠冠状动脉小动脉血管舒张中的参与程度，并阐明其发生的潜在细胞信号转导途径。
从麻醉的小鼠中取出心脏，从对照C57Bl/6J、TRPA1-/-、TRPV1-/-和双敲除小鼠（TRPAV-/-）中分离冠状动脉小动脉。将分离的微血管插管并固定在温度控制的腔室中，使其平衡1小时。在用U46619预收缩的微血管中进行血管反应性研究，以评估丙泊酚对冠状动脉微血管张力的剂量依赖性舒张作用。
丙泊酚诱导的舒张在从TRPV1-/-小鼠获得的血管中不受影响，在从TRPA1-/-小鼠获得的预收缩血管中明显减弱，而在从TRPAV-/-小鼠获得的血管中则完全消失。此外，用L-NAME抑制一氧化氮合酶（NOS）或去除内皮可消除所有小鼠预收缩血管中丙泊酚诱导的降压反应。在没有L-NAME的情况下，用青霉震颤素A抑制大电导钙激活钾通道（BKCa）可明显减弱野生型小鼠血管中丙泊酚介导的舒张，在TRPV1-/-小鼠的血管中减弱程度较小，而在TRPA1-/-或TRPAV-/-小鼠的血管中则无作用。
TRPA1和TRPV1似乎参与了丙泊酚介导的对U46619诱导的小鼠冠状动脉微血管收缩的拮抗作用，这涉及NOS和BKCa的激活。
