Korean J Physiol Pharmacol.  2016 Sep;20(5):441-447. 10.4196/kjpp.2016.20.5.441.

Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase

• Nong L
• Ma J
• Zhang G
• Deng C
• Mao S
• Li H
• Cui J

• KMID: 2350500
• DOI: http://doi.org/10.4196/kjpp.2016.20.5.441

Abstract

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.

Keyword

Dexmedetomidine; Human pulmonary arteries; Nitric oxide; Serotonin; Vasoconstriction

MeSH Terms

Arteries
Dexmedetomidine*
Endothelium
Humans
Indomethacin
Lung
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type III*
Pulmonary Artery
Serotonin
Vasoconstriction*
Yohimbine
Dexmedetomidine
Indomethacin
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type III
Serotonin
Yohimbine

Figure

• 

  Fig. 1 DEX concerntration-dependently induced contraction in endothelium-denuded arteries.*p<0.05 vs. control.

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  Fig. 2 Serotonin induced contraction in the absence and presence of DEX.DEX (0.3~3 nmol.L–1) concerntration-dependently attenuated serotonin-induced contractions. *p<0.05 vs. control.

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  Fig. 3 Inhibitory effect of DEX (3×10–9 mol/L) on serotonin–induced contractions was abolished in the endothelium-denuded arteries.No significant difference was observed between control and DEX pretreated artery rings in endothelium denuded group. *p<0.05 vs. control in endothelium intact group. #p<0.05 vs. Dex with endothelium.

• 

  Fig. 4 Inhibitory effect of DEX (3×10–9 mol/L) on serotonin–induced contractions was abolished in the presence of L-NAME (10–4 mol/L).The comparison was made in pulmonary artery rings with intact endothelium in the absence and presence of L-NAME. *p<0.05 vs. control. #p<0.05 vs. DEX without L-NAME.

• 

  Fig. 5 Inhibitory effect of DEX (3×10–9 mol/L) to serotonin–induced contractions was abolished in the presence of Yohimbine (5×10–8 mol/L).*p<0.05 vs. control. #p<0.05 vs. Dex without Yohimbine.

• 

  Fig. 6 Inhibitory effect of dexmedetomidine (3×10–9 mol/L) to serotonin–induced contractions was not affected in the presence of indomethacin (5×10–6 mol/L).*p<0.05 vs. control. #p<0.05 vs. Dex with indomathcin.

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