Lee Soohee, Hwang Yeran, Park Kyeong-Eon, Bae Sungil, Ok Seong-Ho, Ahn Seung-Hyun, Sim Gyujin, Bae Moonju, Sohn Ju-Tae
Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon-si 51472, Gyeongsangnam-do, Republic of Korea.
Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Jinju-si 52727, Gyeongsangnam-do, Republic of Korea.
Int J Mol Sci. 2024 Mar 5;25(5):3017. doi: 10.3390/ijms25053017.
Dexmedetomidine is widely used to induce sedation in the perioperative period. This study examined the effect of hypothermia (33 and 25 °C) on dexmedetomidine-induced contraction in an endothelium-intact aorta with or without the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME). In addition, the effect of hypothermia on the contraction induced by dexmedetomidine in an endothelium-denuded aorta with or without a calcium-free Krebs solution was examined. The effects of hypothermia on the protein kinase C (PKC), myosin light chain (MLC) phosphorylation, and Rho-kinase membrane translocation induced by dexmedetomidine were examined. Hypothermia inhibited dexmedetomidine-induced contraction in the endothelium-intact aorta with L-NAME or endothelium-denuded aorta. Hypothermia had almost no effect on the dexmedetomidine-induced contraction in the endothelium-denuded aorta with the calcium-free Krebs solution; however, the subsequent contraction induced by the addition of calcium was inhibited by hypothermia. Conversely, the transition from profound hypothermia back to normothermia reversed the hypothermia-induced inhibition of subsequent calcium-induced contractions. Hypothermia inhibited any contraction induced by KCl, PDBu, and NaF, as well as PKC and MLC phosphorylation and Rho-kinase membrane translocation induced by dexmedetomidine. These results suggest that hypothermia inhibits dexmedetomidine-induced contraction, which is mediated mainly by the impediment of calcium influx and partially by the attenuation of pathways involving PKC and Rho-kinase activation.
右美托咪定被广泛用于围手术期诱导镇静。本研究考察了低温（33℃和25℃）对有或无一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯（L-NAME）的完整内皮主动脉中右美托咪定诱导的收缩的影响。此外，还考察了低温对有或无无钙Krebs溶液的去内皮主动脉中右美托咪定诱导的收缩的影响。研究了低温对右美托咪定诱导的蛋白激酶C（PKC）、肌球蛋白轻链（MLC）磷酸化以及Rho激酶膜转位的影响。低温抑制了在有L-NAME的完整内皮主动脉或去内皮主动脉中右美托咪定诱导的收缩。低温对有无钙Krebs溶液的去内皮主动脉中右美托咪定诱导的收缩几乎没有影响；然而，随后添加钙诱导的收缩被低温抑制。相反，从深度低温恢复到正常体温可逆转低温诱导的对随后钙诱导收缩的抑制。低温抑制了由氯化钾、佛波酯和氟化钠诱导的任何收缩，以及右美托咪定诱导的PKC和MLC磷酸化以及Rho激酶膜转位。这些结果表明，低温抑制右美托咪定诱导的收缩，这主要是由钙内流受阻介导的，部分是由涉及PKC和Rho激酶激活的途径的减弱介导的。
