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.

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.

Objective To investigate the effect of dexmedetomidine on 5- HT- induced constrictions of isolated human intrapulmonary arteries and explore the mechanisms. Methods 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 vasoconstractions. The influences of the endothelium removal and various drugs including L-NAME, yohimbine and indomethacin were tested on the effects of dexmedetomidine. Results 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. Conclusion Dexmedetomidine can inhibit 5-HT-induced vasoconstriction of isolated human intrapulmonary arteries probably throughα2-adrenergic acceptor and NO released from the endothelium.

Objective To investigate the effect of dexmedetomidine on 5- HT- induced constrictions of isolated human intrapulmonary arteries and explore the mechanisms. Methods 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 vasoconstractions. The influences of the endothelium removal and various drugs including L-NAME, yohimbine and indomethacin were tested on the effects of dexmedetomidine. Results 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. Conclusion Dexmedetomidine can inhibit 5-HT-induced vasoconstriction of isolated human intrapulmonary arteries probably throughα2-adrenergic acceptor and NO released from the endothelium.

Objective To determine the effect of resveratrol on constrictions of isolated human intrapulmonary arteries and its mechanisms. Methods Intrapulmonary arteries (1-1.5 mm in diameter) were dissected and cut into rings (1.8-2.0 mm in length) under microscope, and were then mounted in a Multi Myograph system. The rings were stimulated with 100 nmol/L U46619, 30 nmol/L endothelin-1, or 60 mmol/L KCl to produce sustained contraction of the intrapulmonary arteries, after which resveratrol was applied cumulatively. Endothelium denudation, L-NAME and indomethecin were used to investigate the effect of resveratrol on constrictions of the isolated arteries, suing DMSO as the control. Results Resveratrol induced concentration-dependent relaxations in endothelium-intact rings that contracted in response to stimulations with U46619, ET-1 and KCl, with pD2 of 3.82 ± 0.20, 3.84 ± 0.57, and 3.68 ± 0.27, Emax of (99.58 ± 0.83)%, 100%, and (99.65 ± 0.98)%, respectively. Treatment of the arterial rings with the eNOS inhibitor L-NAME, but not with indomethecin or endothelium denudation, obviously affected the relaxant effects of resveratrol. Conclusion Resveratrol can concentration-dependently produce relaxant effect on human intrapulmonary arteries independent of the endothelium possibly by promoting synthesis and release of NO.

Objective To determine the effect of resveratrol on constrictions of isolated human intrapulmonary arteries and its mechanisms. Methods Intrapulmonary arteries (1-1.5 mm in diameter) were dissected and cut into rings (1.8-2.0 mm in length) under microscope, and were then mounted in a Multi Myograph system. The rings were stimulated with 100 nmol/L U46619, 30 nmol/L endothelin-1, or 60 mmol/L KCl to produce sustained contraction of the intrapulmonary arteries, after which resveratrol was applied cumulatively. Endothelium denudation, L-NAME and indomethecin were used to investigate the effect of resveratrol on constrictions of the isolated arteries, suing DMSO as the control. Results Resveratrol induced concentration-dependent relaxations in endothelium-intact rings that contracted in response to stimulations with U46619, ET-1 and KCl, with pD2 of 3.82 ± 0.20, 3.84 ± 0.57, and 3.68 ± 0.27, Emax of (99.58 ± 0.83)%, 100%, and (99.65 ± 0.98)%, respectively. Treatment of the arterial rings with the eNOS inhibitor L-NAME, but not with indomethecin or endothelium denudation, obviously affected the relaxant effects of resveratrol. Conclusion Resveratrol can concentration-dependently produce relaxant effect on human intrapulmonary arteries independent of the endothelium possibly by promoting synthesis and release of NO.

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).
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ; Animals ; Arteries* ; Blood Vessels ; Calcium ; Calcium Channels ; Endothelium ; Humans ; Male ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Phenylephrine ; Propofol* ; Pulmonary Artery ; Rats* ; Relaxation ; Serotonin

OBJECTIVETo investigate the reactivity of intrapulmonary arterial rings to vasoactive substances as thromboxane A2 and endothelin-1 in patients with chronic obstructive pulmonary disease (COPD).

METHODSIntrapulmonary 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.

RESULTSThe 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.

CONCLUSIONThe reactivity of intrapulmonary arterial rings is significantly decreased in patients with COPD.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ; pharmacology ; Aged ; Endothelin-1 ; metabolism ; Female ; Humans ; In Vitro Techniques ; Indomethacin ; pharmacology ; Male ; Middle Aged ; Pulmonary Artery ; metabolism ; Pulmonary Disease, Chronic Obstructive ; metabolism ; Thromboxane A2 ; metabolism

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.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ; Arteries ; Calcium ; Calcium Channels ; Constriction ; Endothelium ; Humans* ; Indomethacin ; Myocytes, Smooth Muscle ; Propofol* ; Prostaglandin-Endoperoxide Synthases ; Pulmonary Artery* ; Relaxation ; Vasoconstriction* ; Vasodilation

OBJECTIVETo investigate the effect of dexmedetomidine on 5-HT-induced constrictions of isolated human intrapulmonary arteries and explore the mechanisms.

METHODSLung 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.

RESULTSDexmedetomidine (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.

CONCLUSIONDexmedetomidine can inhibit 5-HT-induced vasoconstriction of isolated human intrapulmonary arteries probably through α2-adrenergic acceptor and NO released from the endothelium.

Adult ; Aged ; Dexmedetomidine ; pharmacology ; Female ; Humans ; In Vitro Techniques ; Male ; Middle Aged ; Pulmonary Artery ; drug effects ; Serotonin ; pharmacology ; Vasoconstriction ; drug effects