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

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.

Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase

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.

Dexmedetomidine inhibits 5-HT-induced intrapulmonary artery vasoconstriction / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of dexmedetomidine on 5-HT-induced constrictions of isolated human intrapulmonary arteries and explore the mechanisms.</p><p><b>METHODS</b>Lung tissue was obtained from patients undergoing surgery for lung carcinoma. Intrapulmonary arteries were dissected and cut into rings, which were mounted in a Multi Myograph system to determine the effect of dexmedetomidine (0.3-3 nmol/L) on 5-HT-induced vasoconstrictions. The influences of the endothelium removal and various drugs including L-NAME, yohimbine and indomethacin were tested on the effects of dexmedetomidine.</p><p><b>RESULTS</b>Dexmedetomidine (0.1-100 nmol/L) did not obviously affect the resting tension of endothelium-intact human intrapulmonary arteries. 5-HT induced concentration-dependent contraction in endothelium-intact intrapulmonary arteries [pD2: 6.11∓0.05, Emax: (102.10∓1.96)%]. In the rings with intact endothelium, dexmedetomidine (0.3-3 nmol/L) significantly attenuated the Emax and pD2 of 5-HT-induced vasoconstriction [pD2: 5.94∓0.03, Emax: (79.96∓1.31)%]. 5-HT also induced concentration-dependent contraction in endothelium-denuded intrapulmonary arteries [pD2: 6.10∓0.07, Emax: (107.40∓3.20)%]. Dexmedetomidine produced no significant effects on the rings with denuded endothelium. The effects of dexmedetomidine on 5-HT-induced vasoconstriction was suppressed by L-NAME and yohimbine, but not by indomethacin.</p><p><b>CONCLUSION</b>Dexmedetomidine can inhibit 5-HT-induced vasoconstriction of isolated human intrapulmonary arteries probably through α2-adrenergic acceptor and NO released from the endothelium.</p>

Role of parecoxib in protection of learning and memory ability in rats with transient global cerebral ischemia/reperfusion inj ury / 实用医学杂志

Objective To explore the role of parecoxib in protection of learning and memory ablility in rats with global cerebral ischemia/reperfusion injury. Methods Male Wistar rats were randomly divided into a sham group (S group), a ischemia/reperfusion group (I/R group), and a ischemia/reperfusion with parecoxib group (I/R+PA group). Global cerebral ischemia was induced by Pulsinelli 4-vessel occlusion. 72 h after reperfusion, Morris water maze was used to assess spatial learning and memory ability for consecutive five days. The histological changes in the hippocampus were detected by Nissl staining. Results As compared with the I/R group, rats in S guoup and I/R+PA group had a significantly shortened escape latency (P<0.05), and had significantly longer dwelling time in the former platform quadrant and more frequent cross-platform movement in the Morris water maze test. Conclusions Parecoxib plays a role in protection of learning and memory ability in rats with global cerebral ischemia/reperfusion injury.

The Relaxant Effect of Propofol on Isolated Rat Intrapulmonary Arteries

Propofol is a widely used anesthetic. Many studies have shown that propofol has direct effects on blood vessels, but the precise mechanism is not fully understood. Secondary intrapulmonary artery rings from male rats were prepared and mounted in a Multi Myograph System. The following constrictors were used to induce contractions in isolated artery rings: high K+ solution (60 mmol/L); U46619 solution (100 nmol/L); 5-hydroxytryptamine (5-HT; 3 micromol/L); or phenylephrine (Phe; 1 micromol/L). The relaxation effects of propofol were tested on high K+ or U46619 precontracted rings. Propofol also was added to induce relaxation of rings preconstricted by U46619 after pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The effects of propofol on Ca2+ influx via the L-type Ca2+ channels were evaluated by examining contraction-dependent responses to CaCl2 in the absence or presence of propofol (10 to 300 micromol/L). High K+ solution and U46619 induced remarkable contractions of the rings, whereas contractions induced by 5-HT and Phe were weak. Propofol induced dose-dependent relaxation of artery rings precontracted by the high K+ solution. Propofol also induced relaxation of rings precontracted by U46619 in an endothelium-independent way. Propofol at different concentrations significantly inhibited the Ca2+-induced contractions of pulmonary rings exposed to high K+-containing and Ca2+-free solution in a dose-dependent manner. Propofol relaxed vessels precontracted by the high K+ solution and U46619 in an endothelium-independent way. The mechanism for this effect may involve inhibition of calcium influx through voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs).

Reactivity of intrapulmonary arterial rings to thromboxane A2 and endothelin-1 is reduced in patients with chronic obstructive pulmonary disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the reactivity of intrapulmonary arterial rings to vasoactive substances as thromboxane A2 and endothelin-1 in patients with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Intrapulmonary arterial rings isolated from patients with normal lung function and COPD were mounted in a Multi Myograph system to determine the reactivity of the intrapulmonary arterial rings to 60 mmol/L KCl, thromboxane A2 analogue U46619 and endothelin-1 before and after preconditioning with the COX synthase inhibitor indomethacin.</p><p><b>RESULTS</b>The reactivity of intrapulmonary arterial rings to U46619 and endothelin-1 was significantly decreased in patients with COPD. The reactivity to U46619 was dramatically decreased in patients with normal lung function after application of indomethacin.</p><p><b>CONCLUSION</b>The reactivity of intrapulmonary arterial rings is significantly decreased in patients with COPD.</p>

Effect of acute hypoxia on contractile function of isolated small pulmonary arteries in patients with moderate chronic obstructive pulmonary disease / 中华麻醉学杂志

Objective To evaluate the effect of acute hypoxia on the contractile function of isolated small pulmonary arteries in patients with moderate chronic obstructive pulmonary disease (COPD).Methods Seven patients with lung cancer,of both sexes,scheduled for elective pulmonary lobectomy,with no pulmonary hypertension and with normal pulmonary function after examination,were included in the study.Six cases were diagnosed as having moderate COPD.Lung tissues 5 cm away from the tumor tissues were taken during operation and the small pulmonary arteries were isolated and divided into 2 groups:control group (n =7) and COPD group (n =6).The contractile amplitude of small pulmonary arteries was detected using vasomotor tone meter under the state of acute hypoxia.Results Contractile amplitude of small pulmonary arteries in response to hypoxic stimulus was significantly decreased in COPD group compared with control group (P ＜ 0.01).Conclusion Acute hypoxia can further reduce the contractile function of isolated small pulmonary arteries in patients with moderate COPD.