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

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.
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

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

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.

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

Gossypol is a kind of yellow polyphenolic compounds extracted from root, stem and seed of the cotton plant. It had received significant attention for its potential application as a male antifertility agent. Then it was used to treat female hormone-dependent diseases, for instance, endometriosis, hysteromyoma, uterine bleeding and dys-menorrheal. Current recent researches showed that gossypol has multiple biological activities, such as anti-inflammatory , antimalarial, antiviral, antioxidant activities and so on, especially the activity to induce tumor cell apoptosis.

This review describes the observations that constitutive ATM activation (CAA) and H2AX phosphoryla-tion (CHP) caused by endogenous oxidants in normal cells as well in tumor cell lines.This review also reported the findings on differences in CAA and CHP on the effects of several agents and growth conditions.

Aim: To study the effects of Clostridium difficile toxin A on the cytotoxity and apoptosis of human hep-atoma cell line SMMC-7721. Methods: Clone inhibiting experiment and MTT calorimetric assay were used to assay SMMC-7721 proliferation. Morphological changes relevant to the apoptosis and the DNA damage were analyzed by transmission electron microscope and single cell gel assay. The number of apoptosis cells and the expression of Bcl-2 and p53 protein were detected by the flow cytometry. Results: 0. 018- 4. 690 mg/L toxin A significantly decreased the colony information of SMMC-7721 cells, and greatly inhibited SMMC-7721 proliferation in a time- and concentration-dependent manner. Morphological changes related to apoptosis were evident under transmission electron microscope and DNA damage was detected by single cell gel assay when SMMC-7721 cultured with 4. 690 mg/L toxin A for 48 h. Toxin A 0. 0734. 690 mg/L induced apoptosis in SMMC-7721 cells from 6. 8% to 41. 8%. In addition, Toxin A 0. 293-4. 690 mg/L significant decreased Bcl-2 protein expression and increased p53 protein expression in SMMC-7721. Conclusion: These results showed that clostridium difficile toxin A had a significantly cytotoxicity in human SMMC-7721 which was attributed to toxin A induced apoptosis.