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OBJECTIVE: To observe whether low concentration (1×10-8 mol·L-1) of ouabain (OUA) can increase the contractility in rat cardiocytes and investigate the Na/K pump signal transduction pathways related to positive inotropic action following the low concentration of OUA. METHODS: On enzymatic isolation of rats ventricular myocytes, the Na+/K+ pump current (Ip) was by whole-cell patch-clamp, in order to observe the low concentration of OUA on Ip. The contraction of a single myocyte was assessed by a video-based motion edge-detection system. (1) To detect and compare the potentiations of 1×10-8-1×10-3 mol·L-1 OUA on the contractility in rat cardiocytes. (2) The cardiocytes were pre-treated with PP2 (1 μmol·L-1), NAC (100 μmol·L-1), PD98059(50 μmol·L-1) for 5 min, and the effects of the signals transduction inhibitors on the positive inotropic effect of 1×10-8 mol·L-1 OUA was recorded. RESULTS: The 1×10-8-1×10-3 mol·L-1 OUA increased the contractility of rat cardiocytes (P0.05). CONCLUSION: The 1×10-8-1×10-3 mol·L-1 OUA could increase the contraction amplitude of cardiocytes in rats in concentration-dependent manner. Positive inotropic effect of OUA in low concentration is related to Na/K pump signal transduction. Multiple signal pathways regulate the positive inotropic effect of 1×10-8 mol·L-1 of OUA, including the Src/ROS signal pathway.
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Aim To investigate the effects of dioscin ( Dio) on rat myocardial contractility. Methods Left ventricular contractile function was measured using the Langendorff non-recirculating mode of isolated rat heart perfusion. Effects of low, middle and high concentra-tion of Dio were investigated by measuring left ventricu-lar systolic pressure ( LVSP ) and left ventricular end diastolic pressure ( LVEDP) . Also, peak rates of rise/fall of left ventricular pressure ( ± dp/dtmax ) of isolated rat heart were calculated. Effects of Dio on intracellu-lar free calcium concentration in rat H9 c2 cells were measured by using the confocal microscopy. Mitochon-drial membrane potential was detected with multifunc-tional microplate reader. Results With 0. 1, 1 μmol · L-1 Dio, LVSP were significantly enhanced from (11. 55 ± 0. 52), (10. 53 ± 0. 28) kPa to (13. 08 ± 0. 72), (12. 53 ±0. 64) kPa(P<0. 01); +dp/dtmax were dramatically increased from ( 0. 38 ± 0. 10 ) , (0. 40 ± 0. 07) kPa·ms-1 to (0. 42 ± 0. 11), (0. 43 ± 0. 02) kPa·ms-1(P<0. 05). With the 10μmol· L-1 Dio, LVSP and + dp/dtmax were both decreased from (12. 13 ± 0. 33) kPa and (0. 42 ± 0. 04) kPa· ms-1 to ( 9. 46 ± 0. 77 ) kPa and ( 0. 24 ± 0. 04 ) kPa ·ms-1 (P <0. 01). With 0. 1, 1, 10 μmol·L-1 Dio, the relative fluorescence intensity of intracellular free calcium concentrations was increased significantly from (16. 62 ± 0. 89) to (21. 48 ± 0. 80), (25. 68 ± 0. 69) and (19. 84 ± 0. 66)(P <0. 01)respectively. 0. 1, 1μmol·L-1 Dio showed no significant effects on the mitochondrial membrane potential of rat H9 c2 cells, while with effects of 10 μmol·L-1 Dio, the ra-tio of JC-1 monomer and J-aggregates was changed from (1. 14 ± 0. 03) to (1. 35 ± 0. 06)(P<0. 01), indica-ting a decrease in the mitochondrial membrane poten-tial. Conclusion Low and middle concentrations of Dio show a positive inotropic effect on isolated rat heart, as the LVSP and + dp/dtmax are enhanced, which may concern with the increase of the intracellu-lar concentration of Ca2+. It will not cause the calcium overload while the intracellular concentration of Ca2+ is increased by low and middle concentration of Dio in the myocytes except high concentration of Dio.
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OBJECTIVE: To design and synthesize the secondary alcohol derivatives of ligustrazine and to investigate their inotropic effects in normal isolated rat hearts. METHODS: 3, 6-Dimethyl-2, 5-pyrazine formaldehyde was obtained from oxidizing 2, 5-dihydroxymethyl-3, 6-dimethylpyrazine, and then reacted with Grignard reagent in tetrahydrofuran, to get the secondary alcohol derivatives. Normal isolated rat hearts were perfused by the Langendorff technique and observed for the effects of these compounds on left ventricular inotropic effects. RESULTS: These compounds were verified by 1H-NMR, 13C-NMR, IR and MS spectra, and they induced positive inotropic effects in normal isolated rat hearts without affecting heart rate. CONCLUSION: Series of ligustrazine secondary alcohol derivatives produced positive inotropic effect in normal isolated rat hearts. The derivatives with longer alkyl substituents showed less positive inotropic effect.