Effects of serotonin(5-HT)and noradrenaline(NA)on neuronal activities of the sol-itary tract nucleus(NTS)were investigated in rat medullary slice preparations.After perfusingthe slice with 5-HT,the spontaneous dischar...Effects of serotonin(5-HT)and noradrenaline(NA)on neuronal activities of the sol-itary tract nucleus(NTS)were investigated in rat medullary slice preparations.After perfusingthe slice with 5-HT,the spontaneous discharge was significantly increased in 25(of 43,58.1%)NTS neurons,reduced in 13(30.2%)and not changed in 5(11.7%).After perfusingthe slice with NA,the spontaneous discharge was significantly reduced or even completelyceased in 27(62.8%)neurons,increased in 13(30.2%)and not changed in 3(7%).Therewere 38(88.4%)neurons responding to both 5-HT and NA.From the 38 neurons,21 wereselected for studying the effect of ketanserin.It was found that ketanserin potentiated the ef-fect of NA on spontaneous discharge in 10(47.6%)neurons and attenuated it in 4(19.0%)neurons.These results suggest that there is an interaction between 5-HT receptorand α-adrenoceptor at the NTS level.This interaction may be helpful in explaining themechanism of the central antihypertensive action of ketanserin.展开更多
Aim Baroreflex dysfunction is associated with a higher rate of sudden death after myocardial infarction （MI）. Ketanserin enhances baroreflex function in rats. The present work was designed to examine whether ketan- ...Aim Baroreflex dysfunction is associated with a higher rate of sudden death after myocardial infarction （MI）. Ketanserin enhances baroreflex function in rats. The present work was designed to examine whether ketan- serin improves the post-MI cardiac function and to explore the possible mechanism involved. Methods Spontane- ously hypertensive rats （SHR） were treated with ketanserin （0.3 mg · kg^-1 · d^-l）. Two weeks later, blood pres- sure and baroreflex function were measured, followed by a ligation of the left coronary artery. The expressions of ve- sicular acetylcholine transporter （VAChT） and α7 nicotinic acetylcholine receptor （α7-nAChR） in ischemic myo- cardium, angiogenesis, cardiac function, and left ventricular （LV） remodeling were evaluated subsequently. Re- sults Ketanserin significantly improved baroreflex sensitivity （0.62 ± 0. 21 vs. 0.34 ± 0. 12 ms/mmHg, P 〈 0.01 ） and vagal tonic activity （ heart rate changes in response to atropine, 54.8 ± 16.2 vs. 37.6 ± 13.4 b. p. m. , P 〈 0.01 ） without affecting the blood pressure or basic heart rate in SHR. Treatment of SHR with ketanserin promi- nently improved cardiac function and alleviated LV remodeling, as reflected by increases in the ejection fraction, fractional shortening, and LV systolic pressure as well as decreases in LV internal diameter and LV relative weight. The capillary density, vascular endothelial growth factor expression, and blood flow in the ischemic myocardium were significantly higher in the ketanserin-treated group. In addition, ketanserin markedly increased the expression of VAChT and α7-nAChR in ischemic myocardium. Conclusion Ketanserin improved post-MI cardiac function and angiogenesis in ischemic myocardium. The findings provide a mechanistic basis for restoring baroreflex function using ketanserin in the treatment of MI.展开更多
Background Ketanserin （KT）, a selective serotonin （5-HT） 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method ...Background Ketanserin （KT）, a selective serotonin （5-HT） 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances. Methods Kv1.3 channels were expressed in xenopus oocytes, and currents were measured using the two-microelectrode voltage-clamp technique. Results KCI made a left shift of activation and an inactivation curve of Kv1.3 current and accelerated the activation and inactivation time constant. High extracellular [K^＋] attenuated the blockade effect of KT on Kv1.3 channels. In the presence of KT and KCI the activation and inactivation time constants were not influenced significantly no matter what was administered first. KT did not significantly inhibit Kv1.3 current induced by tetraethylammonium （TEA）. Conclusions KT is a weak blocker of Kv1.3 channels at different concentrations of extracellular potassium and binds to the intracellular side of the channel pore. The inhibitor KT of ion channels is not fully effective in clinical use because of high [K^＋]. and other electrolyte disorders.展开更多
OBJECTIVE Microglia M1/M2 po⁃larization play pro-inflammatory and anti-inflam⁃matory roles,respectively,which is involved in memory decline.There is a close relationship between impaired baroreflex function and memory...OBJECTIVE Microglia M1/M2 po⁃larization play pro-inflammatory and anti-inflam⁃matory roles,respectively,which is involved in memory decline.There is a close relationship between impaired baroreflex function and memory impairment.The present study was designed to investigate whether arterial baroreflex deficiency induced by sinoaortic denervation(SAD)affected inflammation through modulation of M1/M2 polar⁃ization leading to the aggravation of learning and memory disorders in rats.METHODS Adult male SD rats were divided into four groups:the sham control,the SAD,the sham+scopolamine,the SAD+scopolamine.In another experiment,there were also four groups:the sham control,the SAD,the SAD+scopolamine and the SAD+scopolamine+ketanserin.All rats were examined for various behaviors using Morris water maze test,new object recognition test,and light dark shuttle test and Y maze test 4 weeks after sham or SAD surgery.CD16,CD206,IL-10,IL-6,IL-1βand TNF-αfrom hippocampus using Western blotting,immunofluorescence and turbidimetry.RESULTS Compared with the sham+scopol⁃amine,the SAD+scopolamine rats showed the reduced crossing times in Morris water maze test,the longer residence time in dark box during light dark shuttle test,and the decreased alterna⁃tion ratio in Y maze test.The level of CD206,IL-10,T-AOC and GSH was decreased,whereas CD16,IL-6,TNF-α,MDA was increased in the hippocampus of SAD+scopolamine rats.Addi⁃tionally,all the above changes were improved in the SAD+scopolamine+ketanserin rats when compared with the SAD+scopolamine.CONCLU⁃SION Arterial baroreflex dysfunction aggravates learning and memory disorders in rats,which may be related to the polarization of microglia.展开更多
基金Project supported by the National Natural Science Foundation of China N 3880743
文摘Effects of serotonin(5-HT)and noradrenaline(NA)on neuronal activities of the sol-itary tract nucleus(NTS)were investigated in rat medullary slice preparations.After perfusingthe slice with 5-HT,the spontaneous discharge was significantly increased in 25(of 43,58.1%)NTS neurons,reduced in 13(30.2%)and not changed in 5(11.7%).After perfusingthe slice with NA,the spontaneous discharge was significantly reduced or even completelyceased in 27(62.8%)neurons,increased in 13(30.2%)and not changed in 3(7%).Therewere 38(88.4%)neurons responding to both 5-HT and NA.From the 38 neurons,21 wereselected for studying the effect of ketanserin.It was found that ketanserin potentiated the ef-fect of NA on spontaneous discharge in 10(47.6%)neurons and attenuated it in 4(19.0%)neurons.These results suggest that there is an interaction between 5-HT receptorand α-adrenoceptor at the NTS level.This interaction may be helpful in explaining themechanism of the central antihypertensive action of ketanserin.
文摘Aim Baroreflex dysfunction is associated with a higher rate of sudden death after myocardial infarction （MI）. Ketanserin enhances baroreflex function in rats. The present work was designed to examine whether ketan- serin improves the post-MI cardiac function and to explore the possible mechanism involved. Methods Spontane- ously hypertensive rats （SHR） were treated with ketanserin （0.3 mg · kg^-1 · d^-l）. Two weeks later, blood pres- sure and baroreflex function were measured, followed by a ligation of the left coronary artery. The expressions of ve- sicular acetylcholine transporter （VAChT） and α7 nicotinic acetylcholine receptor （α7-nAChR） in ischemic myo- cardium, angiogenesis, cardiac function, and left ventricular （LV） remodeling were evaluated subsequently. Re- sults Ketanserin significantly improved baroreflex sensitivity （0.62 ± 0. 21 vs. 0.34 ± 0. 12 ms/mmHg, P 〈 0.01 ） and vagal tonic activity （ heart rate changes in response to atropine, 54.8 ± 16.2 vs. 37.6 ± 13.4 b. p. m. , P 〈 0.01 ） without affecting the blood pressure or basic heart rate in SHR. Treatment of SHR with ketanserin promi- nently improved cardiac function and alleviated LV remodeling, as reflected by increases in the ejection fraction, fractional shortening, and LV systolic pressure as well as decreases in LV internal diameter and LV relative weight. The capillary density, vascular endothelial growth factor expression, and blood flow in the ischemic myocardium were significantly higher in the ketanserin-treated group. In addition, ketanserin markedly increased the expression of VAChT and α7-nAChR in ischemic myocardium. Conclusion Ketanserin improved post-MI cardiac function and angiogenesis in ischemic myocardium. The findings provide a mechanistic basis for restoring baroreflex function using ketanserin in the treatment of MI.
文摘Background Ketanserin （KT）, a selective serotonin （5-HT） 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances. Methods Kv1.3 channels were expressed in xenopus oocytes, and currents were measured using the two-microelectrode voltage-clamp technique. Results KCI made a left shift of activation and an inactivation curve of Kv1.3 current and accelerated the activation and inactivation time constant. High extracellular [K^＋] attenuated the blockade effect of KT on Kv1.3 channels. In the presence of KT and KCI the activation and inactivation time constants were not influenced significantly no matter what was administered first. KT did not significantly inhibit Kv1.3 current induced by tetraethylammonium （TEA）. Conclusions KT is a weak blocker of Kv1.3 channels at different concentrations of extracellular potassium and binds to the intracellular side of the channel pore. The inhibitor KT of ion channels is not fully effective in clinical use because of high [K^＋]. and other electrolyte disorders.
基金Natural Science Foundation of Shandong Province(ZR2017MH048)。
文摘OBJECTIVE Microglia M1/M2 po⁃larization play pro-inflammatory and anti-inflam⁃matory roles,respectively,which is involved in memory decline.There is a close relationship between impaired baroreflex function and memory impairment.The present study was designed to investigate whether arterial baroreflex deficiency induced by sinoaortic denervation(SAD)affected inflammation through modulation of M1/M2 polar⁃ization leading to the aggravation of learning and memory disorders in rats.METHODS Adult male SD rats were divided into four groups:the sham control,the SAD,the sham+scopolamine,the SAD+scopolamine.In another experiment,there were also four groups:the sham control,the SAD,the SAD+scopolamine and the SAD+scopolamine+ketanserin.All rats were examined for various behaviors using Morris water maze test,new object recognition test,and light dark shuttle test and Y maze test 4 weeks after sham or SAD surgery.CD16,CD206,IL-10,IL-6,IL-1βand TNF-αfrom hippocampus using Western blotting,immunofluorescence and turbidimetry.RESULTS Compared with the sham+scopol⁃amine,the SAD+scopolamine rats showed the reduced crossing times in Morris water maze test,the longer residence time in dark box during light dark shuttle test,and the decreased alterna⁃tion ratio in Y maze test.The level of CD206,IL-10,T-AOC and GSH was decreased,whereas CD16,IL-6,TNF-α,MDA was increased in the hippocampus of SAD+scopolamine rats.Addi⁃tionally,all the above changes were improved in the SAD+scopolamine+ketanserin rats when compared with the SAD+scopolamine.CONCLU⁃SION Arterial baroreflex dysfunction aggravates learning and memory disorders in rats,which may be related to the polarization of microglia.
