Aim： To observe effects of angiotensin （Ang） II receptor antagonist （ATI） irbesartan and angiotensin-converting enzyme （ACE） inhibitor perindopril on rat myocardium calcineurin expression and sarcoplasmic retic...Aim： To observe effects of angiotensin （Ang） II receptor antagonist （ATI） irbesartan and angiotensin-converting enzyme （ACE） inhibitor perindopril on rat myocardium calcineurin expression and sarcoplasmic reticulum Ca^2＋-ATPase activity in the model of pressure-overload cardiac hypertrophy. Methods： Forty male adult Sprague Dawley rats were divided into 5 groups One group was treated by sham operation; four groups were myocardium hypertrophy cases caused by banding aortic above renal artery. Drugs were given one week after operation. Group 1： sham group, rats （n=8） were gavaged with normal saline 2 ml/（kg·d） （ig）; Group 2： control group, rats （n=8） were treated with normal saline 2 ml/（kg·d） （ig）; Group 3： rats （n=8） were given perindopril 2 mg/（kg·d） （ig）; Group 4： rats （n=8） were treated with irbesartan 20 mg/（kg·d） （ig）; Group 5： rats （n=8） were given irbesartan 20 mg/（kg·d） plus perindopril 2 mg/（kg·d） （ig）. Morphometric determination, calcineurin expression and sarcoplasmic reticulum Ca^2＋-ATPase activity were done at the end of 6 week of drug intervention. Expression of calcineurin in myocardium was detected by immunohistochemistry. Results： Left ventricular mass index （LVMI）, transverse diameter of myocardial cell （TDM）, calcineurin activity were remarkably decreased after drug intervention and this decrease was most remarkable in the combination drug therapy group. Sarcoplasmic reticulum Ca^2＋-ATPase activity was increased after drug intervention, especially in the combined drug therapy group. Calcineurin expression in myocardium was remarkably decreased after drug intervention. LVMI was positively correlated with TDM and calcineurin, negatively correlated with sarcoplasmic reticulum Ca^2＋-ATPase. Conclusion： These data suggest that irbesartan and perindopril inhibit cardiac hypertrophy through the increased activity of sarcoplasmic reticulum Ca^2＋-ATPase and decreased expression of calcineurin. Their combination had better effects on regressing of ventricular hypertrophy.展开更多
AIM: To discuss the expression of α-adrenoreceptors in pancreatic cancer cell lines PC-2 and PC-3 and the effects of α1- and α2-adrenoreceptor antagonists, yohimbine and urapidil hydrochloride, on the cell lines in...AIM: To discuss the expression of α-adrenoreceptors in pancreatic cancer cell lines PC-2 and PC-3 and the effects of α1- and α2-adrenoreceptor antagonists, yohimbine and urapidil hydrochloride, on the cell lines in vitro. METHODS: We cultured the human ductal pancreatic adenocarcinoma cell lines PC-2 and PC-3 and analyzed the mRNA expression of α1- and α2-adrenergic receptors by reverse transcription polymerase chain reaction (RT-PCR). The effects of yohimbine and urapidil hydrochloride on cell proliferation were assessed by 3-(4,5-dimethylthiasol-2-yl)- 2,4,-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay and flow cytometry (FCM). RESULTS: PC-2 expressed mRNA in α1- and α2- adrenoreceptors. MTT assays showed that urapidil hydrochloride had no effect on PC-3 cell lines. However, exposure to urapidil hydrochloride increased DNA synthesis in PC-2 cell lines as compared to the control group. PC-2 cell lines were sensitive to both drugs. The proliferation of the 2 cell lines was inhibited by yohimbine. Cell proliferation was inhibited by yohimbine via apoptosis induction. CONCLUSION: The expression of α1- and α2- adrenoreceptors is different in PC-2 and PC-3 cell lines, which might be indicative of their different functions. The α2-adrenoceptor antagonist, yohimbine, can inhibit theproliferation of both cell lines and induce their apoptosis, suggesting that yohimbine can be used as an anticancer drug for apoptosis of PC-2 and PC-3 cells.展开更多
Aim The biophore of uroselective α_1-adrenoceptor antagonist was studied byusing Apex-3D software on an 02 Silicon Graphics Computer Station. Methods Five known antagonists(Indoramin, GG-818, RS100975, R-YM12167, and...Aim The biophore of uroselective α_1-adrenoceptor antagonist was studied byusing Apex-3D software on an 02 Silicon Graphics Computer Station. Methods Five known antagonists(Indoramin, GG-818, RS100975, R-YM12167, and KMD-3213), which possess both good selectivity and highaffinities to prostate and α_1-AR subtype, were chosen for building the biophore. Using anautomatic filtering software for obtaining reasonable biophores, the filter parameters wereselected: P (probability) > 0.8, active (number of active compounds) ≥ 4, and size (descriptorcenter) ≥ 3. Results Three biophores conformed to the requirements, each of whom contained a basiccenter, an aromatic ring center and H-site according to the structure-activity relationships ofknown α_1-adrenoceptor antagonist. Conclusion The biophore model developed by computer simulationwith Apex-3D software can be used to design and synthesize a new α_1-adrenoceptor antagonist withhigh activity and low side effect.展开更多
Objective To investigate the effect of phenylephrine （an α-adrenergic agonist） on alveolar fluid clearance （AFC） in ventilator-induced lung injury and the possible mechanism involved. Methods A total of 170 mal...Objective To investigate the effect of phenylephrine （an α-adrenergic agonist） on alveolar fluid clearance （AFC） in ventilator-induced lung injury and the possible mechanism involved. Methods A total of 170 male Wistar rats were randomly allocated into 17 groups （n= 10） using ran- dom number tables. Short-term （40 minutes） mechanical ventilation with high tidal volume （HVT） was per- formed to induce lung injury, impair active Na＋ transport and lung liquid clearance in the rats. Unventilated rats served as controls. To demonstrate the effect of phenylephrine on AFC, phenylephrine at different con- centrations （1×10^-5, 1 ×10^-6, 1×10^-7, 1×10^-8, and 1×10^-9 mol/L） was injected into the alveolar space of the HVT ventilated rats. To identify the influence of adrenergic antagonists, Na＋ channel, and microtubular sys- tem on the effect of phenylephrine, phenylephrine at 1×10^-5mol/L combined with prazosin （an α1-adrener- gic antagonist, 1×10^-4 mol/L）, yohimbine （an α2-adrenergic antagonist, 1×10^-4 mol/L）, atenolol （a β1- adrenergic antagonist, 1×10^-5 mol/L）, ICI- 118551 （an β2-adrenergic antagonist, 1×10^-5 mol/L）, amiloride （a Na＋ channel blocker, 51×10^-4mol/L）, ouabain （a Na＋/K＋-ATPase blocker, 5~×10^-4mol/L）, colchicine （a mi- crotubular disrupting agent, 0.25 mg/100 g body weight）, or β-lumicolchicine （an isomer of colchicine, 0.25 mg/100 g body weight） were perfused into the alveolar space of the rats ventilated with HVT for 40 minutes. AFC and total lung water content were measured. Results Basal AFC in control rats was （17.47±2.56）%/hour, which decreased to （9.64± 1.32）%/hour in HVT ventilated rats （P=0.003）. The perfusion of phenylephrine at 1 ×10^-8, 1×10^-7, 1×10^-6, and 1×10^-5 mol/L significantly increased the AFC in HVT ventilated rats （all P〈0.05）. This effect of phenylephrine on AFC was suppressed by prazosin, atenolol, and ICI-118551 in HVT ventilated rats by 53%, 31%, and 37%, respectively （all P〈0.05）. The AFC-stimulating effect of phenylephrine was lowered by 33% and 42% with amiloride and ouabain, respectively （both P〈0.05）. Colchicine significantly inhibited the effect of phenylephrine （P=0.031）. Conclusion Phenylephrine could increase the AFC in HVT-ventilated rats and accelerate the ab- sorption of pulmonary edema.展开更多
Despite significant therapeutic advances, patients with chronic heart failure （HF） remain at high risk of morbidity and mortality. Sacubitill valsartan （previously known as LCZ696） is a new oral agent approved for...Despite significant therapeutic advances, patients with chronic heart failure （HF） remain at high risk of morbidity and mortality. Sacubitill valsartan （previously known as LCZ696） is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the fast in class angiotensin receptor neprilysin inhibitor （ARNI） since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin Ⅱ receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides （NPs）, bradykinin, endothelin and angiotensin II （Ang-II）. Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-Ⅱ （with opposite biological actions）. So, a combined inhibition of these both systems （Sacubitril / valsartan） may enhance the benefits of NPs effects in HF （natriuresis, diuresis, etc） while Ang-Ⅱ receptor is inhibited （reducing vasoconstriction and aldosterone release）. In a large clinical trial （PARADIGM-HF with 8442 patients）, this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF （compared to enalapril）. This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.展开更多
Objective: to report the application of GPIIb/IIIa antagonist (Integrilin) in peri percutaneous transluminal catheter angioplasty and stent implantation in Chinese. Method: Twenty one patients who underwent percutan...Objective: to report the application of GPIIb/IIIa antagonist (Integrilin) in peri percutaneous transluminal catheter angioplasty and stent implantation in Chinese. Method: Twenty one patients who underwent percutaneous transluminal catheter angioplasty(PTCA) and stent implantation were included. After arterial puncture, integrilin was injected at dose of 180ug/kg, and then maintained at 2μg/kg·min for 18 hours. Asprine, plavix(clopidogrel) and heparin were used at the same time. ACT, PT, KPTT and blood routine were routinely monitored. Results: All sheaths were drawn out 2 to 4 hours after the procedure.. There was no severe complication such as hematoma, acute and subacute thrombosis in coronary artery, or thrombocytopenia. ACT returned to less than 150 seconds in 2 hours in 15 patients; in 4 hours in 6 patients. There was no significant difference between the pre and post procedure value of PT and platelet count. KPTT was significantly higher than pre procedure value at 2 hours after the procedure .No recurrence of angina pectoris was observed in the first nine patients within one year follow up, and no restenosis occurred in stents in the five patients who had coronary angiography one year later. Conclusion: Application of GPIIb/IIIa receptor antagonist (Integrilin) in peri percutaneous transluminal catheter angioplasty and stent implantation in combination with aspirin and plavix could significantly reduce the dosage and duration of heparin with benefit of shortening the indwelling time of sheaths, but did not increase risk of bleeding or lead to thrombosis in stent.展开更多
Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6...Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit＋ bosentan group and Nit＋ losartan group. Nitroglycerin tolerance was induced by 2- day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg－ 1· d－ 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg－ 1· d－ 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit＋ losartan group and Nit＋ bosentan group compared with Nit group [(31.95± 4.45 )％ vs (21.00± 3.69 )％ , P< 0.01 and (33.18± 6.16 )％ vs (21.00± 3.69 )％ , P< 0.01 ,respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50％ of the maximal response to SNP) was found in tolerant group[(34± 10) nmol/ L,P < 0.01 .The ET- 1 amounts in plasma and vascular tissue were markedly increased by 54％ and 60％ in Nit group compared with those in control group(P< 0.01).The ET- 1 amounts in plasma and vascular tissue were decreased by 30％ and 37％ in Nit＋ losartan group compared with those in Nit group (P< 0.01). Conclusion. Endothelin receptor antagonist and angiotensinⅡ receptor antagonist could prevent against the Nit tolerance .展开更多
Being a great threaten for human health, obesity has become a pandemic chronic disease. There have been several therapeutic treatments for this social health issue, including diet and exercise therapy, medication and ...Being a great threaten for human health, obesity has become a pandemic chronic disease. There have been several therapeutic treatments for this social health issue, including diet and exercise therapy, medication and surgery, among which the diet is still the most common way. However, none of these therapeutic measures available is ideal, making it necessary to find an effective medical treatment. The endocannabinoid system, which is well known for its contributions in certain mental processes such as relaxation, amelioration of pain and anxiety, and sedation initiation, has been recently reported to play an essential role in regulating appetite and metabolism to maintain energy balance, leading to the belief that endocannabinoid system is closely related to obesity. This new discovery deepens our understanding of obesity, and provides us with a new direction for clinical obesity treatment. Rimonabant is an antagonist for CB1, and has entered the market in some countries. However, although effective as an anti-obesity drug, rimonabant also causes obviously adverse side-effects, thus is being doubted and denied for medical usage.展开更多
AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome.METHODS:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was adminis...AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome.METHODS:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was administered to rats chronically treated with either△^(9)-tetrahydrocannabinol(THC)or vehicle.Subjects were then injected with either SR141716A or vehicle and behavior was observed for 1 h.RESULTS:Administration of the cannabinoid receptor antagonist SR141716A to animals chronically treated with THC as described by Tsou et al(1995)produced a profound withdrawal syndrome.Treatment with dopamine antagonists did not attenuate cannabinoid precipitated withdrawal syndrome in THC tolerant animals while the agonists increased the syndrome.CONCLUSION:It is unlikely that the dopaminergic system plays a major role in mediating the behavioral aspects of the cannabinoid withdrawal syndrome.展开更多
文摘Aim： To observe effects of angiotensin （Ang） II receptor antagonist （ATI） irbesartan and angiotensin-converting enzyme （ACE） inhibitor perindopril on rat myocardium calcineurin expression and sarcoplasmic reticulum Ca^2＋-ATPase activity in the model of pressure-overload cardiac hypertrophy. Methods： Forty male adult Sprague Dawley rats were divided into 5 groups One group was treated by sham operation; four groups were myocardium hypertrophy cases caused by banding aortic above renal artery. Drugs were given one week after operation. Group 1： sham group, rats （n=8） were gavaged with normal saline 2 ml/（kg·d） （ig）; Group 2： control group, rats （n=8） were treated with normal saline 2 ml/（kg·d） （ig）; Group 3： rats （n=8） were given perindopril 2 mg/（kg·d） （ig）; Group 4： rats （n=8） were treated with irbesartan 20 mg/（kg·d） （ig）; Group 5： rats （n=8） were given irbesartan 20 mg/（kg·d） plus perindopril 2 mg/（kg·d） （ig）. Morphometric determination, calcineurin expression and sarcoplasmic reticulum Ca^2＋-ATPase activity were done at the end of 6 week of drug intervention. Expression of calcineurin in myocardium was detected by immunohistochemistry. Results： Left ventricular mass index （LVMI）, transverse diameter of myocardial cell （TDM）, calcineurin activity were remarkably decreased after drug intervention and this decrease was most remarkable in the combination drug therapy group. Sarcoplasmic reticulum Ca^2＋-ATPase activity was increased after drug intervention, especially in the combined drug therapy group. Calcineurin expression in myocardium was remarkably decreased after drug intervention. LVMI was positively correlated with TDM and calcineurin, negatively correlated with sarcoplasmic reticulum Ca^2＋-ATPase. Conclusion： These data suggest that irbesartan and perindopril inhibit cardiac hypertrophy through the increased activity of sarcoplasmic reticulum Ca^2＋-ATPase and decreased expression of calcineurin. Their combination had better effects on regressing of ventricular hypertrophy.
基金The Natural Science Foundation of Shaanxi Province, No. 2006C209
文摘AIM: To discuss the expression of α-adrenoreceptors in pancreatic cancer cell lines PC-2 and PC-3 and the effects of α1- and α2-adrenoreceptor antagonists, yohimbine and urapidil hydrochloride, on the cell lines in vitro. METHODS: We cultured the human ductal pancreatic adenocarcinoma cell lines PC-2 and PC-3 and analyzed the mRNA expression of α1- and α2-adrenergic receptors by reverse transcription polymerase chain reaction (RT-PCR). The effects of yohimbine and urapidil hydrochloride on cell proliferation were assessed by 3-(4,5-dimethylthiasol-2-yl)- 2,4,-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay and flow cytometry (FCM). RESULTS: PC-2 expressed mRNA in α1- and α2- adrenoreceptors. MTT assays showed that urapidil hydrochloride had no effect on PC-3 cell lines. However, exposure to urapidil hydrochloride increased DNA synthesis in PC-2 cell lines as compared to the control group. PC-2 cell lines were sensitive to both drugs. The proliferation of the 2 cell lines was inhibited by yohimbine. Cell proliferation was inhibited by yohimbine via apoptosis induction. CONCLUSION: The expression of α1- and α2- adrenoreceptors is different in PC-2 and PC-3 cell lines, which might be indicative of their different functions. The α2-adrenoceptor antagonist, yohimbine, can inhibit theproliferation of both cell lines and induce their apoptosis, suggesting that yohimbine can be used as an anticancer drug for apoptosis of PC-2 and PC-3 cells.
文摘Aim The biophore of uroselective α_1-adrenoceptor antagonist was studied byusing Apex-3D software on an 02 Silicon Graphics Computer Station. Methods Five known antagonists(Indoramin, GG-818, RS100975, R-YM12167, and KMD-3213), which possess both good selectivity and highaffinities to prostate and α_1-AR subtype, were chosen for building the biophore. Using anautomatic filtering software for obtaining reasonable biophores, the filter parameters wereselected: P (probability) > 0.8, active (number of active compounds) ≥ 4, and size (descriptorcenter) ≥ 3. Results Three biophores conformed to the requirements, each of whom contained a basiccenter, an aromatic ring center and H-site according to the structure-activity relationships ofknown α_1-adrenoceptor antagonist. Conclusion The biophore model developed by computer simulationwith Apex-3D software can be used to design and synthesize a new α_1-adrenoceptor antagonist withhigh activity and low side effect.
基金Supported by the Natural Science Foundation of Liaoning Province (201202245)
文摘Objective To investigate the effect of phenylephrine （an α-adrenergic agonist） on alveolar fluid clearance （AFC） in ventilator-induced lung injury and the possible mechanism involved. Methods A total of 170 male Wistar rats were randomly allocated into 17 groups （n= 10） using ran- dom number tables. Short-term （40 minutes） mechanical ventilation with high tidal volume （HVT） was per- formed to induce lung injury, impair active Na＋ transport and lung liquid clearance in the rats. Unventilated rats served as controls. To demonstrate the effect of phenylephrine on AFC, phenylephrine at different con- centrations （1×10^-5, 1 ×10^-6, 1×10^-7, 1×10^-8, and 1×10^-9 mol/L） was injected into the alveolar space of the HVT ventilated rats. To identify the influence of adrenergic antagonists, Na＋ channel, and microtubular sys- tem on the effect of phenylephrine, phenylephrine at 1×10^-5mol/L combined with prazosin （an α1-adrener- gic antagonist, 1×10^-4 mol/L）, yohimbine （an α2-adrenergic antagonist, 1×10^-4 mol/L）, atenolol （a β1- adrenergic antagonist, 1×10^-5 mol/L）, ICI- 118551 （an β2-adrenergic antagonist, 1×10^-5 mol/L）, amiloride （a Na＋ channel blocker, 51×10^-4mol/L）, ouabain （a Na＋/K＋-ATPase blocker, 5~×10^-4mol/L）, colchicine （a mi- crotubular disrupting agent, 0.25 mg/100 g body weight）, or β-lumicolchicine （an isomer of colchicine, 0.25 mg/100 g body weight） were perfused into the alveolar space of the rats ventilated with HVT for 40 minutes. AFC and total lung water content were measured. Results Basal AFC in control rats was （17.47±2.56）%/hour, which decreased to （9.64± 1.32）%/hour in HVT ventilated rats （P=0.003）. The perfusion of phenylephrine at 1 ×10^-8, 1×10^-7, 1×10^-6, and 1×10^-5 mol/L significantly increased the AFC in HVT ventilated rats （all P〈0.05）. This effect of phenylephrine on AFC was suppressed by prazosin, atenolol, and ICI-118551 in HVT ventilated rats by 53%, 31%, and 37%, respectively （all P〈0.05）. The AFC-stimulating effect of phenylephrine was lowered by 33% and 42% with amiloride and ouabain, respectively （both P〈0.05）. Colchicine significantly inhibited the effect of phenylephrine （P=0.031）. Conclusion Phenylephrine could increase the AFC in HVT-ventilated rats and accelerate the ab- sorption of pulmonary edema.
文摘Despite significant therapeutic advances, patients with chronic heart failure （HF） remain at high risk of morbidity and mortality. Sacubitill valsartan （previously known as LCZ696） is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the fast in class angiotensin receptor neprilysin inhibitor （ARNI） since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin Ⅱ receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides （NPs）, bradykinin, endothelin and angiotensin II （Ang-II）. Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-Ⅱ （with opposite biological actions）. So, a combined inhibition of these both systems （Sacubitril / valsartan） may enhance the benefits of NPs effects in HF （natriuresis, diuresis, etc） while Ang-Ⅱ receptor is inhibited （reducing vasoconstriction and aldosterone release）. In a large clinical trial （PARADIGM-HF with 8442 patients）, this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF （compared to enalapril）. This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.
文摘Objective: to report the application of GPIIb/IIIa antagonist (Integrilin) in peri percutaneous transluminal catheter angioplasty and stent implantation in Chinese. Method: Twenty one patients who underwent percutaneous transluminal catheter angioplasty(PTCA) and stent implantation were included. After arterial puncture, integrilin was injected at dose of 180ug/kg, and then maintained at 2μg/kg·min for 18 hours. Asprine, plavix(clopidogrel) and heparin were used at the same time. ACT, PT, KPTT and blood routine were routinely monitored. Results: All sheaths were drawn out 2 to 4 hours after the procedure.. There was no severe complication such as hematoma, acute and subacute thrombosis in coronary artery, or thrombocytopenia. ACT returned to less than 150 seconds in 2 hours in 15 patients; in 4 hours in 6 patients. There was no significant difference between the pre and post procedure value of PT and platelet count. KPTT was significantly higher than pre procedure value at 2 hours after the procedure .No recurrence of angina pectoris was observed in the first nine patients within one year follow up, and no restenosis occurred in stents in the five patients who had coronary angiography one year later. Conclusion: Application of GPIIb/IIIa receptor antagonist (Integrilin) in peri percutaneous transluminal catheter angioplasty and stent implantation in combination with aspirin and plavix could significantly reduce the dosage and duration of heparin with benefit of shortening the indwelling time of sheaths, but did not increase risk of bleeding or lead to thrombosis in stent.
文摘Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit＋ bosentan group and Nit＋ losartan group. Nitroglycerin tolerance was induced by 2- day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg－ 1· d－ 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg－ 1· d－ 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit＋ losartan group and Nit＋ bosentan group compared with Nit group [(31.95± 4.45 )％ vs (21.00± 3.69 )％ , P< 0.01 and (33.18± 6.16 )％ vs (21.00± 3.69 )％ , P< 0.01 ,respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50％ of the maximal response to SNP) was found in tolerant group[(34± 10) nmol/ L,P < 0.01 .The ET- 1 amounts in plasma and vascular tissue were markedly increased by 54％ and 60％ in Nit group compared with those in control group(P< 0.01).The ET- 1 amounts in plasma and vascular tissue were decreased by 30％ and 37％ in Nit＋ losartan group compared with those in Nit group (P< 0.01). Conclusion. Endothelin receptor antagonist and angiotensinⅡ receptor antagonist could prevent against the Nit tolerance .
基金supported by the Study Grant (2007) for Medical Students of Second Military Medical University,China
文摘Being a great threaten for human health, obesity has become a pandemic chronic disease. There have been several therapeutic treatments for this social health issue, including diet and exercise therapy, medication and surgery, among which the diet is still the most common way. However, none of these therapeutic measures available is ideal, making it necessary to find an effective medical treatment. The endocannabinoid system, which is well known for its contributions in certain mental processes such as relaxation, amelioration of pain and anxiety, and sedation initiation, has been recently reported to play an essential role in regulating appetite and metabolism to maintain energy balance, leading to the belief that endocannabinoid system is closely related to obesity. This new discovery deepens our understanding of obesity, and provides us with a new direction for clinical obesity treatment. Rimonabant is an antagonist for CB1, and has entered the market in some countries. However, although effective as an anti-obesity drug, rimonabant also causes obviously adverse side-effects, thus is being doubted and denied for medical usage.
文摘AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome.METHODS:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was administered to rats chronically treated with either△^(9)-tetrahydrocannabinol(THC)or vehicle.Subjects were then injected with either SR141716A or vehicle and behavior was observed for 1 h.RESULTS:Administration of the cannabinoid receptor antagonist SR141716A to animals chronically treated with THC as described by Tsou et al(1995)produced a profound withdrawal syndrome.Treatment with dopamine antagonists did not attenuate cannabinoid precipitated withdrawal syndrome in THC tolerant animals while the agonists increased the syndrome.CONCLUSION:It is unlikely that the dopaminergic system plays a major role in mediating the behavioral aspects of the cannabinoid withdrawal syndrome.
