Vitexin protects against cardiac hypertrophy via inhibiting calcineurin and CaMKII signaling pathways.

Vitexin is a flavone glycoside isolated from the leaf of Crataeguspinnatifida Bunge, the utility of which has been demonstrated in several cardiovascular diseases. However, its role in cardiac hypertrophy remains unclear. In the present study, we aimed to determine whether vitexin prevents cardiac hypertrophy induced by isoproterenol (ISO) in cultured neonatal rat ventricular myocytes in vitro and pressure overload-induced cardiac hypertrophy in mice in vivo. The results revealed that vitexin (10, 30, and 100 µM) dose-dependently attenuated cardiac hypertrophy induced by ISO in vitro. Furthermore, vitexin (3, 10, and 30 mg kg(-1)) prevented cardiac hypertrophy induced by transverse aortic constriction as assessed by heart weight/body weight, left ventricular weight/body weight and lung weight/body weight ratios, cardiomyocyte cross-sectional area, echocardiographic parameters, and gene expression of hypertrophic markers. Further investigation demonstrated that vitexin inhibited the increment of the resting intracellular free calcium induced by ISO. Vitexin also inhibited the expression of calcium downstream effectors calcineurin-NFATc3 and phosphorylated calmodulin kinase II (CaMKII) both in vitro and in vivo. Taken together, our results indicate that vitexin has the potential to protect against cardiac hypertrophy through Ca2+-mediated calcineurin-NFATc3 and CaMKII signaling pathways.

Inhibition of 2-aminoethoxydiphenyl borate-induced rat atrial ectopic activity by anti-arrhythmic drugs.

BACKGROUND/AIMS: 2-aminoethoxydiphenyl borate (2-APB) provokes spontaneous mechanical activity in isolated rat left atria. The present study is to characterize 2-APB-induced ectopic activity in rat atria and to investigate the inhibition of 2-APB-induced ectopic activity by anti-arrhythmic drugs. METHODS: 2-APB-induced ectopic activity was measured through an isometric force transducer connected to a multichannel acquisition and analysis system. Intracellular [Ca2+](i) was measured with fluorescence laser scanning confocal microscopy. Voltage-dependent L- type Ca2+ currents were recorded by using patch-clamp technique. RESULTS: 2-APB dose-dependently increased the ectopic activity of left atria at 1, 5, 10, 20, 50 microM. Anti-arrhythmic drugs, quinidine (10 microM), lidocaine (10 microM), verapamil (5 microM), and amiodarone (50 microM, 100 microuM) inhibited 2-APB-induced ectopic activity. 2-APB-induced ectopic activity was inhibited by Ca2+-free bath, Na+/Ca2+ exchanger blockers, 3',4'-dichlorobenzamil hydrochloride (DHC) and Ni2+, not by non-selective cation channel blocker Gd3+. 2-APB also induced ectopic contractions in ventricular tissue straps and the ectopic contractions were inhibited by quinidine, verapamil and DHC. Lidocaine, verapamil and DHC inhibited 2-APB-induced increase of intracellular Ca2+ concentration in cardiomyocytes. Low molecular weight heparin inhibited phenylephrine (PE)-induced but not 2-APB -induced atria ectopic activity, and the pattern of 2-APB-induced ectopic activity was continuous, distinct from the discontinuous activity induced by PE. CONCLUSION: 2-APB-induced atria ectopic activity was inhibited by classic anti-arrhythmic drugs quinidine, lidocaine, verapamil, amiodarone, and Na+/Ca2+ exchanger blockers. It can be used for testing agents able to affect any of Na+, Ca2+ channel, Na+/Ca2+ exchanger without selectivity.

[Regularity of sugar-uptake in human red blood cells].

Lyophilization of human red blood cells has important significance in clinical application. Some sugars, especially trehalose, can be more tolerant of some organism or cells to dry environments, But, how to bring sugars into cells is a challenge. This study was aimed to investigate the regularity of sugar-uptake in human red blood cells. The absorption rate of trehalose and glucose in red blood cells, free hemoglobin level and erythrocyte deformation index were determined at different incubation temperature (4, 25 and 37 degrees C), different sugar concentration (0, 0.2, 0.4, 0.6, 0.8 and 1 mol/L) and different incubation time (1, 3, 5, 7 and 9 hours). The results showed that with increase of temperature and extracellular sugar concentration, the uptake of sugar in red blood cells also increased, the intracellular trehalose and glucose concentrations were over 30 mmol/L and 40 mmol/L respectively. The effects of incubation time on uptake of trehalose and glucose were different. With prolonging of incubation time, the uptake of trehalose showed firstly increase and then decrease, however, the uptake of glucose showed a constant increase. But the loading process had side-effect on free hemoglobin and maximum deformation index (MAXDI) of red blood cells, especially for trehalose, which mainly come from high osmotic pressure. It is concluded that the uptake of sugars in red blood cells is closely dependent on incubation temperature, extracellular sugar concentration and incubation time. In certain condition, the efficiency of sugar uptake is very high, but this process also damages red blood cells so as to affect the application of sugars in lyophilization of red blood cells. The research in the future should focus on how to deal with the relation between cell injury and uptake efficiency of sugar in red blood cells.