Prevalence of cigarette use and addiction among Chinese females by age and province: Findings from nationwide China Health Literacy Survey during 2018-19.

BACKGROUND: The prevalence of cigarette smoking among women is significantly different from that of men, however, cigarette use by women is little known. The study aims to describe cigarette use prevalence and patterns among Chinese females by age and province. METHODS: This study was based on the 2018 China Health Literacy Survey (2018 CHLS), a nationally representative cross-sectional study, and our analysis included 43,319 female participants aged 20-69 with valid data. The prevalence of cigarette use was estimated overall by sociodemographic factors and weighted based on the census population data. The logistic regression model was conducted to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk factors associated with cigarette use and dependency. RESULTS: In China, the estimated female current cigarette use prevalence was 1.85%, with over half of the population suffering from tobacco dependence (7.34 million). Jilin Province has the highest cigarette prevalence among women (10.59%), while Fujian Province has the lowest (0.27%). Participants over 60 years old (aOR=1.61, 95%CI=1.20-2.14), single (aOR=1.54, 95%CI=1.07-2.21), with primary education (aOR=1.93, 95%CI=1.47-2.52) were more likely to smoke. The age of smoking initiation among women intergenerational advanced, and compared to the cigarette users without tobacco dependence, those who have tobacco dependence start smoking earlier in all age groups (25.69 years vs. 19.36 years, p<0.001). CONCLUSIONS: The cigarette use prevalence among Chinese women was 1.85%, and there are significant differences among provinces. We noted a trend of women initiating smoking at increasingly younger ages, particularly among those with tobacco dependence.

Efficacy of varenicline or bupropion and its association with nicotine metabolite ratio among smokers with COPD.

BACKGROUND AND OBJECTIVE: Nicotine metabolic ratio (NMR) has been associated with nicotine metabolism and smoking characteristics. However, there are few studies on the potential association between NMR and smoking cessation efficacy in smokers with chronic obstructive pulmonary disease (COPD) in China or elsewhere. METHODS: This study was a stratified block randomized controlled trial for smoking cessation in Chinese smokers with COPD. NMR was used as a stratification factor; slow metabolizers were defined as those with NMR <0.31, and normal metabolizers as those with NMR ≥0.31. Participants were randomly assigned to the varenicline or bupropion group. Follow-up visits were conducted at 1, 2, 4, 6, 9, 12 and 24 weeks. RESULTS: Two hundred twenty-four participants were recruited and analysed from February 2019 to June 2022. In normal metabolizers, the 9-12 weeks continuous abstinence rate of varenicline (43.1%) was higher than in bupropion (23.5%) (OR = 2.47, 95% CI 1.05-5.78, p = 0.038). There was no significant difference in abstinence rates between treatment groups in slow metabolizers (54.1% vs. 45.9%, OR = 1.39, 95% CI 0.68-2.83, p = 0.366). For slow metabolizers, the total score of side effects in the varenicline group was significantly higher than the bupropion group (p = 0.048), while there was no significant difference in side effects between groups for normal metabolizers (p = 0.360). CONCLUSION: Varenicline showed better efficacy than bupropion in normal metabolizers, and bupropion showed equivalent efficacy in slow metabolizers with less side effects. According to our study, NMR provides a better justification for both scientific research and tailoring optimal pharmacotherapy for smoking cessation among smokers in COPD.

Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS).

Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).

Prevalence of tobacco dependence and associated factors in China: Findings from nationwide China Health Literacy Survey during 2018-19.

Background: Tobacco dependence is the key barrier to successful smoking cessation. However, little is known about its prevalence, sociodemographic characteristics and determinants. We aimed to estimate the prevalence, associated factors and burden of tobacco dependence in China. Methods: During 2018-2019, the nationally representative 2018 China Health Literacy Survey (2018 CHLS) invited 87,708 participants to participate using a multistage stratified sampling method from 31 provinces (or equivalent) in mainland China, and 84,839 participants aged 20-69 with valid data were included in the analysis. We diagnosed tobacco dependence based on international criteria (ICD-10, DSM-4) and tailored to Chinese population according to China Clinical Guideline for Tobacco Cessation (2015 version). The prevalence of tobacco dependence was estimated overall and by sociodemographic factors. The Logistic regression was conducted to estimate odds ratios (OR) and 95% confidence intervals (CIs) for tobacco dependence and success of smoking cessation (being ex-smokers), with different levels of adjustment. These were used to estimate the total number of adults who were tobacco dependent in China. Findings: In China, the estimated prevalence of current smoking was 25.1%, significantly higher in men than in women (47.6% vs 1.9%). The prevalence of current smoking varied approximately 3-fold (12.9% to 37.9%) across 31 provinces of China. Among general population aged 20-69 years, the prevalence of tobacco dependence was 13.1% (95% CI:12.2-14.1). Among current smokers, the prevalence of tobacco dependence was 49.7% (46.5-52.9%), with no difference between men and women (49.7% vs 50.8%). The prevalence of tobacco dependence was associated significantly with smoking intensity, defined by pack-years (1.62 [1.54-1.70] per 10 pack-years), cigarettes smoked per day (2.01 [1.78, 2.27] per 10 cigarettes), and smoking starting age (0.93 [0.90, 0.97] per 5 years). Given smoking intensity, the prevalence of tobacco dependence also varied by age, gender, certain socioeconomic status and regions. Compared with those without tobacco dependence, ever smokers with tobacco dependence were less likely to be ex-smokers (2.88, 2.59-3.21). In China, 183.5 (170.4-197.4) million adults (177.5 million were men) were tobacco dependent in 2018. Interpretation: In China, tobacco dependence is highly prevalent, with approximately half of current smokers being addictive, highlighting the need for coordinated effort to improve awareness, diagnosis and treatment of tobacco dependence. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), National Key R&D Program of China (grant no 2017YFC1309400), and National Natural Science Foundation of China (grant no 81720108001). Note: Chinese translation of abstract is available in appendix section.

The experience of tobacco withdrawal symptoms among current smokers and ex-smokers in the general population: Findings from nationwide China Health Literacy Survey during 2018-19.

Objective: To clarify the extent to which smokers in the general population experience tobacco withdrawal symptoms and whether such experience differs in those who continue to smoke and those who stopped smoking. Methods: We included relevant questions in the nationally-representative China Health Literacy Survey (CHLS) conducted in 2018-2019. Among 87,028 participants, there were 22,115 ever-smokers aged 20-69 years who provided information on their smoking history and their experience of tobacco withdrawal symptoms. Multivariate logistic regressions were conducted to explore the association between withdrawal symptoms and other variables. Results: Among ever-smokers, there were 19,643 (88.8%) current smokers and 2,472 (11.2%) ex-smokers. Among current smokers, 61.3% reported having tried to quit smoking in the past. Overall, 61.1% of current smokers reported experiencing withdrawal symptoms: 69.9% of those who tried to quit smoking in the past and 47.5% of those who did not. A lower proportion of ex-smokers experienced withdrawal symptoms (46.3%) and the difference remained significant after controlling for demographic characteristics (OR = 1.76, 95% CI 1.62-1.93, P < 0.001). The most commonly reported withdrawal symptoms in both current smokers and ex-smokers were craving, restlessness and anxiety. In the multivariable-adjusted analyses, those who experienced withdrawal symptoms when they tried to quit smoking (OR: 2.05, 95% CI: 1.86-2.27) were less likely to successfully quit. Conclusions: The clinical picture of the tobacco withdrawal syndrome is the same in current smokers and in ex-smokers, but ex-smokers are less likely to have experienced it. The experience of discomfort when unable to smoke is common and seems likely to be a major factor contributing to maintaining smoking behavior not just among individuals seeking help with quitting smoking, but among smokers generally.

Mechanism of uncoupling protein 2­mediated myocardial injury in hypothermic preserved rat hearts.

In the present study, the alterations in uncoupling protein 2 (UCP2) expression following hypothermic preservation in rat hearts were investigated. Isolated rat hearts were preserved in Celsior solution for 3­12 h followed by 60 min of reperfusion. The cardiac function was evaluated using the Langendorff perfusion system. UCP2 and silent mating type information regulation 2 homolog 1 (SIRT1) proteins were detected by western blot analysis. The ATP production and mitochondrial reactive oxygen species (ROS) levels were assessed. Subsequent to preservation in ice­cold Celsior solution for 3­12 h, the UCP2 protein expression in rat hearts was observed to increase in a time­dependent manner. The UCP2 inhibitor genipin inhibited the hypothermic preservation­induced cardiac dysfunction, prevented a decline in ATP production induced by 9 h of preservation, however had no effect on the hypothermic preservation­induced increase in mitochondrial ROS levels. Compared with the control group, the SIRT1 protein expression in rat hearts reduced following hypothermic preservation. Compared with the 9­h preservation group, Celsior solution supplemented with the SIRT1 activator resveratrol (20 or 40 µmol/l) inhibited UCP2 protein overexpression, prevented the decline in ATP production and resulted in an improvement cardiac function. The SIRT1 inhibitor EX­527 abolished the resveratrol­induced inhibition of UCP2 overexpression and cardiac protection in the hypothermic preserved rat heart. These observations suggest that downregulation of UCP2 expression in the hypothermic preserved rat heart in part initiated the protective mechanism via the SIRT1 pathway.

[Roles of PIK3R1 gene in development of hepatocellular carcinoma].

OBJECTIVE: To investigate the roles of phosphatidylinositol 3 kinase regulatory subunit alpha (PIK3R1）gene in the development of hepatocellular carcinoma （HCC）. METHODS: Surgical specimens of liver cancer and corresponding pericancerous liver tissue were collected from 20 patients with hepatocellular carcinoma. Expression of p85α, encoded by PIK3R1, in HCC tissue specimens was detected by Western blotting and immunohistochemistry. HCC HepG2 cells were transfected with PIK3R1 siRNA or PIK3R1-cDNA. The expression of PIK3R1 in transfected HepG2 cells or control cells were detected by real-time PCR. Cell proliferation was evaluated by MTT, colony formation assays and flow cytometry respectively. The expression of PI3K/AKT pathway-related proteins were detected by Western blotting. RESULTS: The expression of p85α in liver tissue was higher than that in pericancerous tissues (1.27±0.58 vs 0.99±0.47，t=-3.25，P<0.05）. The expression of PIK3R1 was decreased by 0.19±0.03 fold in PIK3R1siRNA-transfected HepG2 cells(t=46.77，P<0.05)，and increased by 32.36±3.33 fold in PIK3R1 cDNA -transfected cells（t=-16.31， P<0.05）. MTT result showed that PIK3R1 siRNA inhibited growth of HepG2 cells （0.611±0.072 vs 0.807±0.059，t=3.65，P<0.05），while PIK3R1 cDNA increased the cell growth（0.937±0.060 vs 0.693±0.065，t=-4.78，P<0.05）. PIK3R1 siRNA transfected cells presented lower colony-forming efficiency than control group（3.8%±0.84% vs 15.0%±2.3%，t=7.92，P<0.05），while PIK3R1 cDNA transfected cells had higher colony-forming efficiency than control group (23.6%±3.4% vs 12.0%±1.5%，t=-5.40，P<0.05）. PIK3R1 siRNA reduced the ratio of S phase cells（13.9%±0.015% vs 32.9%±0.07%，t=45.97，P<0.01, while PIK3R1 cDNA increased S phase cells（56.33%±0.024% vs 31.94%±0.042%，t=-8.73，P<0.01）. PIK3R1 increased the level of p-AKT and decreased p53 level. CONCLUSION：p85α is highly expressed in HCC，and PIK3R1 gene may promote proliferation of HepG2 cells by activating PI3K/AKT pathway.

Puerarin protects human umbilical vein endothelial cells against high glucose-induced apoptosis by upregulating heme oxygenase-1 and inhibiting calpain activation.

The aim of this study was to investigate whether puerarin protects against high glucose (HG)-induced apoptosis by suppressing calpain activation in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to normal glucose (NG) (5.5 mm) or HG (33 mm) for 48 h; then, apoptosis and caspase-3 activity were determined. The expression of heme oxygenase-1 (HO-1) mRNA was evaluated by RT-PCR analysis. The activation of calpain and HO activity were also assessed. Compared with the NG group, exposure of HUVECs to HG for 48 h resulted in significant increases in calpain and caspase-3 activity as well as apoptosis, which were prevented by co-incubation with puerarin (1-100 µm) in a concentration-dependent manner. HO-1 mRNA expression and HO activity were decreased in HUVECs treated with HG for 48 h. Compared with the group exposed to HG alone, co-incubation of HUVECs with puerarin and HG induced increases in HO-1 mRNA expression and HO activity. The HO-1 inhibitor protoporphyrin IX zinc (II) abolished the inhibitory effect of puerarin on HG-induced calpain and caspase-3 activation, as well as apoptosis. The data show that puerarin protects against HG-induced endothelial cell apoptosis by a mechanism involving upregulation of HO-1 expression and inhibition of calpain activity.

[Effect of AT1 receptor on changes of tyrosine hydroxylase-immunoreactivity in rostral ventrolateral medulla induced by brain cholinergic stimuli in rats].

OBJECTIVE: To investigate the effect of AT1 receptor on the changes of tyrosine hydroxylase-immunoreactivity (TH-IR) in rostral ventrolateral medulla (RVLM) induced by brain cholinergic stimuli in rats. METHODS: Male SD rats were randomly divided into 4 groups: NS + CBC group, Los + CBC group, Los + NS group and NS + NS group. AT1 was blocked by pretreatment of 20 µg losartan in Los + CBC and Los + NS groups; intracerebroventricular injection of 0.5 µg carbachol was used for cholinergic stimuli in NS + CBC and Los + CBC groups; normal saline (NS) was used for control. The output amount of natrium in kidney, glomerular filtration rate (GFR) and renal plasma flow (PRF) were observed. The changes of TH-IR in the RVLM were observed by immunohistochemistry. RESULT: In NS + CBC group carbachol induced potent natriuresis, after pretreatment of losartan the natriuretic effect was partially inhibited in Los + CBC group. Both the number and optical density of TH-IR positive neurons in NS + CBC group were markedly increased than those in NS + NS group (P < 0.05); while those in Los + CBC group were significantly lower than those in NS+CBC group (P < 0.05). Intracerebroventricular injection of carbachol and losartan had no effect on GFR and RPF(P > 0.05). CONCLUSION: The results suggest that cholinergic stimuli can induce potent natriuresis and increase the activity of adrenergic neurons in the RVLM; the above effects can be down regulated by blockade of brain AT1 receptor.

[Effect of nitric oxide synthase inhibitors on the changes of hemodynamic parameters and aortic tension induced by septic shock in rats].

AIM: To investigate the effect of three types of nitric oxide synthase inhibitors on the changes of hemodynamic parameters and thoracic aorta tension induced by septic shock in rats. METHODS: We used cecal ligation and puncture (CLP) method to establish septic shock in rats, and the three types of nitric oxide synthase inhibitors were injected after CLP. The carotid artery was cannulated and connected to a pressure transducer to determine mean arterial blood pressure (MABP). Ventricular dynamic parameters were determined following intraventricular cannulation via the carotid artery, including heart rate (HR), left ventricular developed pressure (LVDP), maximal rise/fall velocity of ventricular pressure (+/- dP/dt(max)). Isolated thoracic rings were mounted on an organ bath and the tension of the vessel was recorded. RESULTS: (1) After using L-NAME, AMG and 7-NI the mortality decreased to 50.0%, 37.5%, and 42.1%, respectively (from 65.2% in septic shock rats); (2) The MABP in septic shock rats partly recovered after using the NOS inhibitors, all ventricular dynamic parameters partly recovered after using the inhibitors; (3) The hyporeactivity of endothelium-denuded aortic rings to vasoconstrictors induced by septic shock was partly recovered by pretreatment with the inhibitors. However, only L-NAME or 7-NI could inhibit the decrease of vasoconstriction induced by septic shock in endothelium-intact aortic rings. CONCLUSION: The three types of nitric oxide synthase inhibitors can improve the hemodynamic parameters and vasoconstriction responsiveness of endothelium-denuded aorta of septic shock rats. Furthermore, L-NAME and 7-NI improve the responsiveness of endothelium-intact aorta.

[Vascular effect of extract from mulberry leaves and underlying mechanism].

OBJECTIVE: To investigate the vascular activity of extract from mulberry leaves (EML) on rat thoracic aorta and the underlying mechanism. METHODS: Isolated thoracic rings of Sprague-Dawley rats were mounted on the organ bath and the tension of the vessel was recorded. RESULT: (1) EML produced a concentration-dependent vasorelaxation of aorta preconstricted by high K(+) (60 mmol/L) or 10(-6) mol/L phenylephrine (PE) in endothelium-intact and endothelium-denuded arteries. (2) EML at EC(50) concentration reduced the calcium dose-response curve. (3) After incubation of aorta with verapamil, EML induced vasocontraction of aorta preconstricted by PE, which was abolished by ruthenium red. CONCLUSION: The vascular effect of EML is biphasic, the vasorelaxation is greater than the vasocontraction. The vasorelaxation induced by EML may be mediated by inhibition of voltage-and receptor-dependent calcium channels in vascular smooth muscle cells, while the vasocontraction is via activation of ryanodine receptor in endoplasmic reticulum.

[The alterations of nitric oxide synthase activity of ventricular cardiac muscle of rats in two septic shock models].

AIM: To observe the differences of hemodynamics and nitric oxide synthase(NOS) activity of ventricular cardiac muscle in two septic shock models and explore the possible mechanism. METHODS: Two rat models of septic shock[lipopolysaccharide(LPS)-induced and cecal ligation and puncture (CLP)-induced septic shock] were used. The hemodynamic parameters and nitric oxide synthase activity of ventricular cardiac muscle were measured. RESULTS: The hemodynamic parameters in CLP-induced model were increased in the early stage and decreased in the late stage while in LPS-induced model the parameters showed the same change of the CLP late stage. Both LPS model and CLP model (late stage) showed significant increase in NOS activity, but there was no difference between the two models. After treatment of the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME), the parameters of CLP-late stage and LPS model increased significantly. The NOS activity reached the highest level in the CLP-middle stage. The production of nitrite/nitrate decreased significantly in LPS model and CLP model(late stage) after treatment of L-NAME, but the nitrite/nitrate produced by constitutive NOS in LPS model was higher than CLP model(late stage). CONCLUSION: The increase of the NOS activity may be the main reason to lead to the depression of the hemodynamic parameters. Inducible NOS may play the leading role in the LPS model while cNOS and iNOS have the same effect in the CLP model.

[Comparison of vasodilatation effect between quercetin and rutin in the isolated rat thoracic aorta].

OBJECTIVE: To determine the possible difference in vasodialtation effect of quercetin and rutin. METHODS: The isolated rat thoracic aorta was treated with phenylephrine (PE), and the effects of quercetin and rutin on the preconstricted aorta rings with or without endothelium were determined by organ bath technique. Nitric oxide synthase inhibitor L-N(G)-nitroarginine methyl-ester (L-NAME), guanylyl cyclase inhibitor methylene blue, cyclooxygenase inhibitor indomethacin were used to explore the mechanism. RESULTS: Quercetin (10-160 micromol/L) caused vasorelaxation of aorta rings preconstricted with PE in endothelium-intact and denuded aorta rings in a dose-dependent manner. Rutin(10-160 micromol/L) caused dose-dependent vasorelaxation in endothelium-intact rings preconstricted with phenylephrine, but not in denuded aorta rings. The maximal response (Rmax) values calculated from vasorelaxation curves of quercetin and rutin were (77.20+/-6.11)% and (44.28+/-7.48)%, respectively. There was no difference between median effective concentration (EC(50)) values of quercetin and rutin. Pretreatment with L-NAME (0.1 mmol/L) abolished the vasorelaxation by rutin,but did not influence the vasodilating effect of quercetin in endothelium-intact rings. Pretreatment with methylene blue (10 mmol/L) canceled the vasorelaxation both by quercetin and rutin. Pretreatment with indomethacin (10 micromol/L) attenuated the vasodilatation of quercetin, but did not affect the vascular effect of rutin. CONCLUSION: The vasodilatation effect of quercetin is more potent than rutin. The vasodilatation effect of quercetin might be mediated by guanylyl cyclase and cyclooxygenase-dependent pathway, while the vasodilatation by rutin might be via nitric oxide-guanylyl cyclase pathway.

Endothelium-dependent and direct relaxation induced by ethyl acetate extract from Flos Chrysanthemi in rat thoracic aorta.

The aims of the present study were to investigate the vasoactive effects of ethyl acetate extract from Flos Chrysanthemi (FCE) and its mechanisms on the rat thoracic aorta. FCE (9.4-150 mg/L) caused a concentration-dependent relaxation on endothelium-intact rings precontracted with phenylephrine (PE, 10(-6)M) or a high level of K+ (6x10(-2)M). By removal of endothelium, the effect was not abolished but reduced significantly. N(G)-nitro-l-arginine methyl ester (l-NAME) (10(-4) M), methylene blue (10(-5) M) significantly inhibited the effect of FCE. Meanwhile, NO synthase of aorta in FCE group was markedly elevated versus the control. However, indomethacin did not influence FCE effect. SKF-525A combined with l-NAME had the same effect as l-NAME. Tetraethylammonium, BaCl2, 4-aminopyridine, 5-HD and propranolol also did not influence the vascular effect of FCE, but glibenclamide significantly attenuated its vasodilation. FCE did not reduce PE-induced transient contraction in Ca(2+)-free medium, but inhibited PE-induced contraction in K(+)-free solution or Ca2+ caused contraction after PE induced a stable contraction in Ca(2+)-free solution. It is concluded that FCE induced both endothelium-dependent and -independent relaxation. NO and cGMP-mediated pathway are likely involved in the endothelium-dependent relaxation, whereas inhibition of voltage-dependent Ca2+ channel, receptor-operate Ca2+ channel and activation of K(ATP) contribute in part to the endothelium-independent relaxation.

Rutin-induced endothelium-dependent vasorelaxation in rat aortic Rings and the underlying mechanism.

The aim of the present study was to determine the possible mechanism by which rutin causes vasodilatation in isolated thoracic aorta rings from the rat. The effects of rutin on rings preconstricted with phenylephrine, with or without endothelium, were determined using an organ bath technique. The mechanism was explored by measuring the effects of the nitric oxide synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), the guanylyl cyclase inhibitor methylene blue, the cyclooxygenase inhibitor indomethacin, the ATP-sensitive K+channel blocker glibenclamide and the beta-adrenoceptor antagonist propranolol. Rutin at the range of 10-160 mumol/L caused dose-dependent vasorelaxation in preconstricted endothelium-intact rings, but had no effect on rings without endothelium. The maximal response calculated from the vasorelaxation curves of rutin was 44.28 plus or mines 7.48%. Pretreatment with L-NAME (0.1 mmol/L), methylene blue (10 mumol/L), glibenclamide (10 mmol/L) or indomethacin (10 mmol/L) attenuated the vasorelaxation induced by rutin in endothelium-intact rings. Glibenclamide (10 mmol/L) enhanced the vasorelaxation of rutin. Propranolol (10 mumol/L) did not block the effect of rutin. The results indicate that vasorelaxation is induced by rutin via the nitric oxide-guanylyl cyclase pathway and a prostaglandin-mediated mechanism, as well as activation of the ATP-sensitive potassium channel.