Dexmedetomidine-Induced Contraction Involves CPI-17 Phosphorylation in Isolated Rat Aortas

Abstract

Dexmedetomidine, a highly selective α-2 adrenoceptor agonist, produces vasoconstriction, which leads to transiently increased blood pressure. The goal of this study was to investigate specific protein kinases and the associated cellular signal pathways responsible for the increased calcium sensitization induced by dexmedetomidine in isolated rat aortas, with a particular focus on phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17). The effect of Y-27632 and chelerythrine on the dexmedetomidine-induced intracellular calcium concentration ([Ca2+]i) and tension were assessed using fura-2-loaded aortic strips. The effects of rauwolscine, Y-27632, chelerythrine, and ML-7 hydrochloride on the dexmedetomidine-induced phosphorylation of CPI-17 or of the 20-kDa regulatory light chain of myosin (MLC20) were investigated in rat aortic vascular smooth muscle cells. The effects of rauwolscine, Y-27632, and chelerythrine on the membrane translocation of Rho-kinase and protein kinase C (PKC) phosphorylation induced by dexmedetomidine were assessed. Y-27632 and chelerythrine each reduced the slopes of the [Ca2+]i-tension curves of dexmedetomidine-induced contraction, and Y-27632 more strongly reduced these slopes than did chelerythrine. Rauwolscine, Y-27632, chelerythrine, and ML-7 hydrochloride attenuated the dexmedetomidine-induced phosphorylation of CPI-17 and MLC20. Taken together, these results suggest that dexmedetomidine-induced contraction involves calcium sensitization, which appears to be mediated by CPI-17 phosphorylation via Rho-kinase or PKC.

Long-Term High-Altitude Hypoxia and Alpha Adrenoceptor-Dependent Pulmonary Arterial Contractions in Fetal and Adult Sheep

“…We then sought to evaluate the role of α 2 -AR to cause further contraction as occurs in pre-stimulated pulmonary vasculature of dog (Shebuski et al, 1987) and rat aorta (Ok et al, 2016), or whether the arteries will relax as described in pig pulmonary arteries (Pepke-Zaba et al, 1993) and fetal sheep pulmonary vasculature (Magnenant et al, 2003). Figure 3B shows the dose-response curves of fetal normoxic arteries treated with incremental doses of dexmedetomidine that were pre-stimulated with 10 μM serotonin.…”

A Lipid Emulsion Reverses Toxic-Dose Bupivacaine-Induced Vasodilation during Tyrosine Phosphorylation-Evoked Contraction in Isolated Rat Aortae

“…Aortic rings were isolated and prepared for tension measurements as previously described [ 12 , 33 ]. Male Sprague-Dawley rats weighing 250–300 g were fully anesthetized by inhalation of 100% carbon dioxide.…”

“…RAVSMCs were isolated from rat thoracic aortae by enzymatic dissociation and then cultured in Dulbecco’s modified Eagle’s medium (HyClone, GE Healthcare, Salt Lake City, UT, USA) supplemented with 10% heat-inactivated fetal bovine serum (Gibco, Life Technologies, New York, NY, USA), 2 mM l -glutamine, 100 U/mL penicillin and 100 µg/mL streptomycin as previously described [ 33 ]. The cells were plated onto a 100-mm culture dish and incubated at 37 °C in a humidified atmosphere containing 5% CO 2 , and the medium was changed every alternate day until the cells reached confluence.…”

Effects of dexmedetomidine combined with oxycodone on sedation effect, perioperative inflammatory response and immunity

“…In this study, TNF-α and IL-6 levels at T3, T4, and T5 were increased in the four groups, with the levels in the ODG being lower as compared with those in the OG, DG, and CG, while IL-2 levels at T3, T4, and T5 were decreased in the four groups, with the levels in the ODG being higher as compared with those in the OG, DG, and CG (p < 0.05), coinciding with prior reports (Mo and Qiu 2017). Among these records, the enhanced perioperative inflammation in patients receiving local anesthetized transforaminal endoscopic resection of nucleus pulposus was alleviated by the actions of dexmedetomidine combined with oxycodone, possibly through mechanisms related to dexmedetomidine suppressing stress reactions in such way that postsynaptic receptors were activated, sympathetic nerve activity was reduced, and the excitability in the sympathetic nervous system induced by the operative wound was blocked as well as related to oxycodone lowering the intracellular cyclic adenosine as well as disturbing the e synthesis, and release of inflammatory factors (Ok et al 2016;Wong et al 2018).…”