To study the effect of simulated ischemia-reperfusion (I/R) on If of sinoatrial node (SAN) cellsand the ntervention of KATP channel opener Pinacidil. Methods: The SAN cells of the neonatal rats were detached and pu-ri...To study the effect of simulated ischemia-reperfusion (I/R) on If of sinoatrial node (SAN) cellsand the ntervention of KATP channel opener Pinacidil. Methods: The SAN cells of the neonatal rats were detached and pu-rified 2 d efore the experiment. The experimental animals were randomly divided into the control group, group of simulatedI/R, group intervened with KATP channel opener Pinacidil (P + I/R) and group intervened with KATP channel blockingagent 5-HD (5-HD + P + I/R & 5-HD + I/R). The If density of each group was measured by technique of routine whole elldifferent directive potentials, the If density of the SAN cells in I/R group increased significantly, compared with that in thecontrol group ( P ＜ 0.01 ); that in P + I/R group decreased significantly, compared with that in I/R group ( P ＜ 0.01 ); theIf density values in 5-HD + P + I/R group and 5-HD + I/R group increased significantly, compared with that in P + I/Red curve of the SAN cells moved rightwards under ultimate activating potential, half of which was from - 108.0 ± 12.4 to- 89.5 ± 7.2 mV ( P ＜ 0.01 ); compared with that in I/R group, If activated curve of the SAN cells moved leftwards underultimate activating potential, half of which was the range from - 99.5 ± 10.8 mV ( P ＜ 0.05 ); KATP channel blockingagent 5-HD could block the effect of Pinacdil on If activated curve. Conclusion: KATP channel opener Pinacidil can antago-nize the effect of simulated I/R on the If of SAN cells, which may be beneficial to the maintenance of the relative stability ofion steady state and electrophysiological activities under condition of simulated I/R.展开更多
Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic b...Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding(AAB).The effects of natakalim(1,3,9 mg·kg-1·d-1,10 weeks)were assessed on myocardial hypertrophy and heart failure,cardiac histology,vasoactive compounds,and gene expression.Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels.Results Ten weeks after the onset of pressure overload,natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure.Natakalim inhibited the changes of left ventricular haemodynamic parameters,reversed the increase of heart mass index,left ventricular weight index and lung weight index remarkably.Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim.Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats.The content of serum NO and plasma PGI2 was increased,while that of plasma ET-1 and cardiac tissue hydroxyproline,ANP and BNP mRNA was down-regulated in natakalim-treated rats.Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats;however,natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE.Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.展开更多
Objective: To study the effect of KATP channel opener and its possible mechanism on the sinoatrial node cells of neonatal rats which were cultured under simulated ischemia-reperfusion. Methods: Freshly isolated sinoat...Objective: To study the effect of KATP channel opener and its possible mechanism on the sinoatrial node cells of neonatal rats which were cultured under simulated ischemia-reperfusion. Methods: Freshly isolated sinoatrial node (SAN) cells of neonatal rats were purified and cultured for 2 d, and then they were randomly divided into the control, simulated ischemia-reperfusion group (I/R group), group intervened with KATP channel opener pinacidil (P+I/R group), KATP Channel blocking agent 5-HD (5-HD+I/R group), and group with the 2 agents at same time (5-HD+P+I/R group). The survival rate of cells was measured by flow cytometry and the content of intracellular calcium in the cells of each group was detected with laser confocal microscopy. Results: ① The survival rate of SAN cells in I/R group [(51.79±6.28)%] was remarkably significantly lower than in control [(95.08±10.48)%] (P<0.001), and very significantly lower than in P+I/R group [(63.77±5.35)%] (P<0.01), however, those of 5-HD+P+I/R group [(52.88±6.25)%] and 5-HD+I/R group [(53.16±5.35)%] was significantly lower compared with that in P+I/R group (P<0.01); ② When the average fluorescence intensity of sinoatrial node cells in the control was regarded as 100%, the relative fluorescence intensities of each group were: (374±52)% in I/R group, significantly higher than that of control (P<0.01); (162±20)% in P+I/R group, declining significantly than that of I/R group (P<0.01); (385±56)% in 5-HD+P+I/R group and (379±44)% in 5-HD+I/R group, increasing significantly than that of I/R group (P<0.01). Conclusion: ① Simulated ischemia-reperfusion can significantly reduce the survival rate of SAN cells, and can also lead to the overload of intracellular calcium in them. ② KATP channel opener, pinacidil, exerts protective effect on the cells under simulated ischemia-reperfusion, which may be associated with the decrease of intracellular calcium loading in them.展开更多
基金Supported by National Natural Science Foundation of China (No.30070314)
文摘To study the effect of simulated ischemia-reperfusion (I/R) on If of sinoatrial node (SAN) cellsand the ntervention of KATP channel opener Pinacidil. Methods: The SAN cells of the neonatal rats were detached and pu-rified 2 d efore the experiment. The experimental animals were randomly divided into the control group, group of simulatedI/R, group intervened with KATP channel opener Pinacidil (P + I/R) and group intervened with KATP channel blockingagent 5-HD (5-HD + P + I/R & 5-HD + I/R). The If density of each group was measured by technique of routine whole elldifferent directive potentials, the If density of the SAN cells in I/R group increased significantly, compared with that in thecontrol group ( P ＜ 0.01 ); that in P + I/R group decreased significantly, compared with that in I/R group ( P ＜ 0.01 ); theIf density values in 5-HD + P + I/R group and 5-HD + I/R group increased significantly, compared with that in P + I/Red curve of the SAN cells moved rightwards under ultimate activating potential, half of which was from - 108.0 ± 12.4 to- 89.5 ± 7.2 mV ( P ＜ 0.01 ); compared with that in I/R group, If activated curve of the SAN cells moved leftwards underultimate activating potential, half of which was the range from - 99.5 ± 10.8 mV ( P ＜ 0.05 ); KATP channel blockingagent 5-HD could block the effect of Pinacdil on If activated curve. Conclusion: KATP channel opener Pinacidil can antago-nize the effect of simulated I/R on the If of SAN cells, which may be beneficial to the maintenance of the relative stability ofion steady state and electrophysiological activities under condition of simulated I/R.
文摘Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding(AAB).The effects of natakalim(1,3,9 mg·kg-1·d-1,10 weeks)were assessed on myocardial hypertrophy and heart failure,cardiac histology,vasoactive compounds,and gene expression.Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels.Results Ten weeks after the onset of pressure overload,natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure.Natakalim inhibited the changes of left ventricular haemodynamic parameters,reversed the increase of heart mass index,left ventricular weight index and lung weight index remarkably.Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim.Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats.The content of serum NO and plasma PGI2 was increased,while that of plasma ET-1 and cardiac tissue hydroxyproline,ANP and BNP mRNA was down-regulated in natakalim-treated rats.Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats;however,natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE.Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.
基金Supported by National Natural Science Foundation of China (No. 30070314)
文摘Objective: To study the effect of KATP channel opener and its possible mechanism on the sinoatrial node cells of neonatal rats which were cultured under simulated ischemia-reperfusion. Methods: Freshly isolated sinoatrial node (SAN) cells of neonatal rats were purified and cultured for 2 d, and then they were randomly divided into the control, simulated ischemia-reperfusion group (I/R group), group intervened with KATP channel opener pinacidil (P+I/R group), KATP Channel blocking agent 5-HD (5-HD+I/R group), and group with the 2 agents at same time (5-HD+P+I/R group). The survival rate of cells was measured by flow cytometry and the content of intracellular calcium in the cells of each group was detected with laser confocal microscopy. Results: ① The survival rate of SAN cells in I/R group [(51.79±6.28)%] was remarkably significantly lower than in control [(95.08±10.48)%] (P<0.001), and very significantly lower than in P+I/R group [(63.77±5.35)%] (P<0.01), however, those of 5-HD+P+I/R group [(52.88±6.25)%] and 5-HD+I/R group [(53.16±5.35)%] was significantly lower compared with that in P+I/R group (P<0.01); ② When the average fluorescence intensity of sinoatrial node cells in the control was regarded as 100%, the relative fluorescence intensities of each group were: (374±52)% in I/R group, significantly higher than that of control (P<0.01); (162±20)% in P+I/R group, declining significantly than that of I/R group (P<0.01); (385±56)% in 5-HD+P+I/R group and (379±44)% in 5-HD+I/R group, increasing significantly than that of I/R group (P<0.01). Conclusion: ① Simulated ischemia-reperfusion can significantly reduce the survival rate of SAN cells, and can also lead to the overload of intracellular calcium in them. ② KATP channel opener, pinacidil, exerts protective effect on the cells under simulated ischemia-reperfusion, which may be associated with the decrease of intracellular calcium loading in them.
