The Relaxant Effect of Propofol on Isolated Rat Intrapulmonary Arteries

Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine (10~100 µM) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine (30 µM), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-HT2A receptor inhibitor, indicating that ketamine facilitated the activation of 5-HT2A receptors. Anpirtoline and BW723C86, selective agonists of 5-HT1B and 5-HT2B receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-HT2A receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-HT2A receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.

Section: Introductionmentioning

confidence: 99%

Facilitation of serotonin-induced contraction of rat mesenteric artery by ketamine

Park

Noh

Kim

et al. 2016

“…A nitric oxide synthase inhibitor (L-NAME) decreased relaxation of the EPA, but had no effect on the IPA. Our team concluded that no significant difference of Emax was observed in the absence or presence of L-NAME in the rat IPA, the vasodilations were endothelium independent [ 7 ]. In the present study, the maximal vasodilator response was higher in endothelium-intact than -denuded rings, but relaxation of endothelium-denuded rings remained evident, showing that the relaxation response may partly depend on the endothelium.…”

Section: Discussionmentioning

confidence: 99%

“…Another study [ 6 ] compared vasorelaxation induced by propofol in the intrapulmonary artery (IPA) and tehe extrapulmonary artery (EPA) and concluded that the response was significantly greater in the EPA than the IPA at higher drug concentrations. We earlier found that propofol exerted a relaxation effect in isolated rat pulmonary arterial rings [ 7 ]. In contrast, propofol potentiated phenylephrine-induced vasoconstriction in both live dogs and pulmonary arterial rings isolated from dogs [ 8 9 ].…”

Section: Introductionmentioning

confidence: 99%

The bifunctional effect of propofol on thromboxane agonist (U46619)-induced vasoconstriction in isolated human pulmonary artery

Hao

Wang

Kuang

et al. 2017

Self Cite

Propofol is known to cause vasorelaxation of several systemic vascular beds. However, its effect on the pulmonary vasculature remains controversial. In the present study, we investigated the effects of propofol on human pulmonary arteries obtained from patients who had undergone surgery. Arterial rings were mounted in a Multi-Myograph system for measurement of isometric forces. U46619 was used to induce sustained contraction of the intrapulmonary arteries, and propofol was then applied (in increments from 10–300 µM). Arteries denuded of endothelium, preincubated or not with indomethacin, were used to investigate the effects of propofol on isolated arteries. Propofol exhibited a bifunctional effect on isolated human pulmonary arteries contracted by U46619, evoking constriction at low concentrations (10–100 µM) followed by secondary relaxation (at 100–300 µM). The extent of constriction induced by propofol was higher in an endothelium-denuded group than in an endothelium-intact group. Preincubation with indomethacin abolished constriction and potentiated relaxation. The maximal relaxation was greater in the endothelium-intact than the endothelium-denuded group. Propofol also suppressed CaCl2-induced constriction in the 60 mM K+-containing Ca2+-free solution in a dose-dependent manner. Fluorescent imaging of Ca2+ using fluo-4 showed that a 10 min incubation with propofol (10–300 µM) inhibited the Ca2+ influx into human pulmonary arterial smooth muscle cells induced by a 60 mM K+-containing Ca2+-free solution. In conclusion, propofol-induced arterial constriction appears to involve prostaglandin production by cyclooxygenase in pulmonary artery smooth muscle cells and the relaxation depends in part on endothelial function, principally on the inhibition of calcium influx through L-type voltage-operated calcium channels.

“…Our group has done a lot of work on isolated pulmonary arteries [ 26 ], the present study is the first to investigate the effect of DEX on human pulmonary arteries. We showed that DEX (10 –8 ~10 –6 mol/L) caused concentration-dependent contractions in endothelium-denuded human pulmonary arteries; however, DEX had no direct effect on tension in endothelium-intact pulmonary arteries.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase

Nong

Zhang

et al. 2016

Self Cite

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.