Background Stimulation of the heart β3-adrenoceptor （AR） may result in a negative inotropic effect. Being up-regulated, β3-AR plays a more important role in the regulation of cardiac function during heart failure....Background Stimulation of the heart β3-adrenoceptor （AR） may result in a negative inotropic effect. Being up-regulated, β3-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of β3-AR on heart failure has not been fully elucidated. In this study, we used a selective β3-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism. Methods Male Wistar rats were chosen randomly as controls （n=-8）. Isoproterenol induced heart failure rats were randomly divided into ISO group （n=-10） and SR group （n=10）. The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes： the ratio of heart weight to body weight （HW/BW） and the ratio of left ventricular weight to body weight （LVW/BW）, collagen volume fraction （CVF）, left ventricular end diastolic dimension （LVEDd）, left ventricular end systolic dimension （LVESd）, ejection fraction （EF）, fractional shortening （FS） and the ratio of E wave to A wave （E/A）, the mRNA and protein expression of β3-AR and eNOS, and cGMP level in the heart. Results The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group （P〈0.01）, but they were limited in the SR group （P〈0.05 compared with the ISO group）. CVF increased in the ISO group and the SR group （P〈0.01）, but it was significantly attenuated in the SR group （P〈0.01）. LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group （P〈0.01）, while EF and FS were significantly decreased （P〈0.01）. Compar展开更多
Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling,sometimes lifeshortening adverse effects.Antipsychotic-induced cardiotoxicity ...Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling,sometimes lifeshortening adverse effects.Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns.These cardiotoxic effects range from arrhythmia to heart failure in the clinic,with myocarditis/cardiomyopathy,ischemic injuries,and unexplained cardiac lesions as the pathological bases.Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity.This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level.We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity.We propose that third-generation antipsychotics or drug adjuvant therapy,such as cannabinoid receptor modulators that confer dual benefits—i.e.,alleviating cardiotoxicity and improving metabolic disorders—deserve further clinical evaluation and marketing.展开更多
OBJECTIVE: To investigate the effect of electroacupuncture(EA) of acupoints Neiguan(PC 6) and Tianquan(PC 2) on the skin temperature, blood perfusion, and alpha1-and beta2-adrenoreceptor(α1-AR and β2-AR) protein and...OBJECTIVE: To investigate the effect of electroacupuncture(EA) of acupoints Neiguan(PC 6) and Tianquan(PC 2) on the skin temperature, blood perfusion, and alpha1-and beta2-adrenoreceptor(α1-AR and β2-AR) protein and m RNA level in rats with acute myocardial ischemia.METHODS: Thirty male adult Wistar rats [(230 ±20) g] were randomly assigned into five groups(n = 6 each): a control group, sham operation group, model group, model group treated with EA at low frequency(L-EA, 2 Hz, 1 m A) and model group treated with EA at high frequency(H-EA, 100 Hz, 1 m A). The rat model was prepared by ligating the left anterior descending coronary artery. Electroacupuncture was performed at the left Neiguan(PC 6) for 20 min daily for 3 d. After the 3 rd time of the treatment, measurements of skin blood perfusion and temperature in Neiguan(PC 6) and Tianquan(PC 2) in all groups were made by laser speckle contrast imaging and infrared thermal image instrument. Real-time PCR and ELISA were used to measure m RNA level and protein level of α1-AR andβ2-AR in the skin tissues of Neiguan(PC 6) and Tianquan(PC 2), respectively. Serum levels of c Tn T and electrocardiogram were used to identify the state of myocardium.RESULTS: In the group receiving electroacupunture at Neiguan(PC 6), compared with control group,the skin temperature, blood perfusion, and β2-AR m RNA and protein level of model group significantly decreased(P < 0.05), α1-AR m RNA and protein level of model group significantly increased(P < 0.05);compared with model group, the skin temperature,blood perfusion, and β2-AR m RNA and protein level of L-EA significantly increased(P < 0.05), α1-AR m RNA and protein level of L-EA and H-EA significantly decreased(P < 0.05). The same trend has taken place in the former four groups of the Tianquan(PC 2).CONCLUSION: Low-or high-frequency electroacupuncture can improve the skin temperature and blood perfusion which may be induced by decreasingthelevelofα1-ARandincreasingthelevelofβ2-AR of the Neiguan(PC 6) and Tianquan(PC 2) in展开更多
基金This study was supported by grants from the Science and Technology Fund of Heilongjiang Education Bureau(No.11511228)the Innovation Fund of Harbin Medical University for Graduate Students(No.200401060)
文摘Background Stimulation of the heart β3-adrenoceptor （AR） may result in a negative inotropic effect. Being up-regulated, β3-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of β3-AR on heart failure has not been fully elucidated. In this study, we used a selective β3-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism. Methods Male Wistar rats were chosen randomly as controls （n=-8）. Isoproterenol induced heart failure rats were randomly divided into ISO group （n=-10） and SR group （n=10）. The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes： the ratio of heart weight to body weight （HW/BW） and the ratio of left ventricular weight to body weight （LVW/BW）, collagen volume fraction （CVF）, left ventricular end diastolic dimension （LVEDd）, left ventricular end systolic dimension （LVESd）, ejection fraction （EF）, fractional shortening （FS） and the ratio of E wave to A wave （E/A）, the mRNA and protein expression of β3-AR and eNOS, and cGMP level in the heart. Results The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group （P〈0.01）, but they were limited in the SR group （P〈0.05 compared with the ISO group）. CVF increased in the ISO group and the SR group （P〈0.01）, but it was significantly attenuated in the SR group （P〈0.01）. LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group （P〈0.01）, while EF and FS were significantly decreased （P〈0.01）. Compar
基金Supported by National Natural Science Foundation of China,No.82070285 and No.81701861.
文摘Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling,sometimes lifeshortening adverse effects.Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns.These cardiotoxic effects range from arrhythmia to heart failure in the clinic,with myocarditis/cardiomyopathy,ischemic injuries,and unexplained cardiac lesions as the pathological bases.Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity.This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level.We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity.We propose that third-generation antipsychotics or drug adjuvant therapy,such as cannabinoid receptor modulators that confer dual benefits—i.e.,alleviating cardiotoxicity and improving metabolic disorders—deserve further clinical evaluation and marketing.
基金Supported by the Law of Sympathetic Nerve Reaction and Receptor Molecular Response in Relevant Acupoints in Different Myocardial Conditions(No.81373558)
文摘OBJECTIVE: To investigate the effect of electroacupuncture(EA) of acupoints Neiguan(PC 6) and Tianquan(PC 2) on the skin temperature, blood perfusion, and alpha1-and beta2-adrenoreceptor(α1-AR and β2-AR) protein and m RNA level in rats with acute myocardial ischemia.METHODS: Thirty male adult Wistar rats [(230 ±20) g] were randomly assigned into five groups(n = 6 each): a control group, sham operation group, model group, model group treated with EA at low frequency(L-EA, 2 Hz, 1 m A) and model group treated with EA at high frequency(H-EA, 100 Hz, 1 m A). The rat model was prepared by ligating the left anterior descending coronary artery. Electroacupuncture was performed at the left Neiguan(PC 6) for 20 min daily for 3 d. After the 3 rd time of the treatment, measurements of skin blood perfusion and temperature in Neiguan(PC 6) and Tianquan(PC 2) in all groups were made by laser speckle contrast imaging and infrared thermal image instrument. Real-time PCR and ELISA were used to measure m RNA level and protein level of α1-AR andβ2-AR in the skin tissues of Neiguan(PC 6) and Tianquan(PC 2), respectively. Serum levels of c Tn T and electrocardiogram were used to identify the state of myocardium.RESULTS: In the group receiving electroacupunture at Neiguan(PC 6), compared with control group,the skin temperature, blood perfusion, and β2-AR m RNA and protein level of model group significantly decreased(P < 0.05), α1-AR m RNA and protein level of model group significantly increased(P < 0.05);compared with model group, the skin temperature,blood perfusion, and β2-AR m RNA and protein level of L-EA significantly increased(P < 0.05), α1-AR m RNA and protein level of L-EA and H-EA significantly decreased(P < 0.05). The same trend has taken place in the former four groups of the Tianquan(PC 2).CONCLUSION: Low-or high-frequency electroacupuncture can improve the skin temperature and blood perfusion which may be induced by decreasingthelevelofα1-ARandincreasingthelevelofβ2-AR of the Neiguan(PC 6) and Tianquan(PC 2) in
