Dexmedetomidine does not produce vasocontraction on human isolated gastroepiploic artery

Kim, Won-Sung; Baek, Sun‐Yong; Lee, Sang Kwon; Jeon, Tae Yong; Kim, Heeyoung; Shin, Sang Chul

doi:10.4097/kjae.2011.60.6.428

Cited by 3 publications

(2 citation statements)

References 15 publications

(17 reference statements)

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“…Coughlan et al found that higher DEX resulted in constriction of canine distal coronary artery by activation of peripheral α2-AR [ 12 ]. Another study also showed that DEX dosage administered in higher than clinical usage (>1.25 ng/mL) caused contraction of isolated human gastroepiploic arterial rings, while 0.36–1.25 ng/mL of DEX did not enhance the vasoconstriction caused by vasopressin in isolated human gastroepiploic arteries [ 13 ]. Our study present results observed in isolated porcine coronary arteries were consistent with these studies.…”

Section: Discussionmentioning

confidence: 99%

Bidirectional Regulatory Effects of Dexmedetomidine on Porcine Coronary Tone In Vitro

Zhou¹,

Liu

et al. 2017

Med Sci Monit

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BackgroundStudies in vivo have shown that dexmedetomidine (DEX) could protect the myocardium and modulate the coronary blood flow. This study aimed to investigate the direct and concentration-dependent effects of DEX on the tone of porcine coronary artery in vitro and the underlying mechanisms.Material/MethodsDistal branches of the porcine anterior descending coronary arteries were dissected and cut into 3–5 mm rings. The tones of coronary rings in response to cumulative DEX were measured using the PowerLab system. Coronary rings were divided into three groups: 1) endothelium-intact coronary rings without drug pretreatment (control); 2) endothelium-intact coronary rings pretreated with either yohimbine, tetraethylamine (TEA) or NG-nitro-L-arginine methyl ester (L-NAME); and 3) endothelium-denuded coronary rings pretreated with either yohimbine or TEA.ResultsDEX induced coronary ring relaxation at lower concentrations (10−9 to 10−7 M) followed by constriction at higher concentrations (10−6 to 10−5 M). The coronary constrictive effect of higher DEX (10−5 M) was greater in the endothelium-denuded rings than in the endothelium-intact rings. Yohimbine reduced the coronary constrictive effect of DEX at higher concentrations (10−6 to 10−5 M). TEA and L-NAME significantly reduced the coronary relaxing effect of DEX at lower concentrations (10−9 to 10−7 M) in endothelium-intact rings. TEA attenuated the coronary relaxation induced by DEX in endothelium-denuded rings.ConclusionsDEX exerts bidirectional effects on porcine coronary tone. The coronary relaxing effect of DEX at lower concentrations is likely associated with endothelium integrity, NO synthesis and BKCa channel activation, while the coronary constrictive effect of DEX at higher concentrations is mediated by α2 adrenoceptors in the coronary smooth muscle cells.

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Section: Discussionmentioning

confidence: 99%

Bidirectional Regulatory Effects of Dexmedetomidine on Porcine Coronary Tone In Vitro

Zhou¹,

Liu

et al. 2017

Med Sci Monit

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“…Showed that endothelial NOS inhibition is required for the indication of DEX-induced vasoconstriction of arteries, yet venous constriction does not require such treatment [ 21 ]. Yildiz [ 18 ] and Won-Sung Kim et al [ 22 ] indicated that clinical doses of DEX could not induce vasoconstriction in the human internal mammary artery and gastroepiploic artery. These findings are contrary to those of previous clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase

Nong

Zhang

et al. 2016

Korean J Physiol Pharmacol

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Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (α2-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of 10–8~10–6 mol/L, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or 3×10–9 mmol/L) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial α2-adrenoceptor and nitric oxide synthase.

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Calcium sensitization involved in dexmedetomidine-induced contraction of isolated rat aorta

Kim

Sung

et al. 2011

Can. J. Physiol. Pharmacol.

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Dexmedetomidine, a full agonist of the α2B-adrenoceptor that is mainly involved in vascular smooth muscle contraction, is primarily used for analgesia and sedation in intensive care units. High-dose dexmedetomidine produces hypertension in children and adults. The goal of this in vitro study was to investigate the role of the calcium (Ca(2+)) sensitization mechanism involving Rho-kinase, protein kinase C (PKC), and phosphoinositide 3-kinase (PI3-K) in mediating contraction of isolated rat aortic smooth muscle in response to dexmedetomidine. The effect of dexmedetomidine on the intracellular Ca(2+) level ([Ca(2+)]i) and tension was measured simultaneously. Dexmedetomidine concentration-response curves were generated in the presence or absence of the following antagonists: rauwolscine, Y 27632, LY 294002, GF 109203X, and verapamil. Dexmedetomidine-induced phosphorylation of PKC and membrane translocation of Rho-kinase were detected with Western blotting. Rauwolscine, Y 27632, GF 109203X, LY 294002, and verapamil attenuated dexmedetomidine-induced contraction. The slope of the [Ca(2+)]i-tension curve for dexmedetomidine was higher than that for KCl. Dexmedetomidine induced phosphorylation of PKC and membrane translocation of Rho-kinase. These results suggest that dexmedetomidine-induced contraction involves a Ca(2+) sensitization mechanism mediated by Rho-kinase, PKC, and PI3-K that is secondary to α2-adrenoceptor stimulation in rat aortic smooth muscle.

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Dexmedetomidine does not produce vasocontraction on human isolated gastroepiploic artery

Cited by 3 publications

References 15 publications

Bidirectional Regulatory Effects of Dexmedetomidine on Porcine Coronary Tone In Vitro

Bidirectional Regulatory Effects of Dexmedetomidine on Porcine Coronary Tone In Vitro

Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase

Calcium sensitization involved in dexmedetomidine-induced contraction of isolated rat aorta

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