Activation of cardiac sympathetic afferent reflex results in the increase of sympathetic activity. Serotonin (5-HT) activates cardiac sympathetic afferent through stimulating 5-HT3 receptors, the aim of present study is to test whether 5-HT3 receptor antagonists protect against cardiac hypertrophy. Cardiac hypertrophy induced by TAC for 4 weeks in mice was significantly inhibited by administration of 5-HT3 receptor antagonists, ondansetron (2.5 mg/kg, ip.) or tropisetron (2.5 mg/kg, ip.). Histological analysis revealed that the increased cardiac fibrosis in hypertrophic heart was relieved by ondansetron or tropisetron treatment. Ondansetron or tropisetron reduced the elevated plasma level of noradrenalin in mice with cardiac hypertrophy. Ondansetron and tropisetron had no effect on cardiomyocte hypertrophy induced by phenylephrine treatment in vitro. Finally, we took tropisetron as the representative drug and examined the effects of tropisetron on the desensitization of cardiac β-adrenergic receptor in rat treated with abdominal aortic banding (AB). Results showed that tropisetron restored the desensitization of cardiac β-adrenergic receptor in AB-treated rats. In conclusion, 5-HT3 receptor antagonists protected against cardiac hypertrophy and restored the desensitization of cardiac adrenergic responsiveness, the mechanism in which may be through reducing the sympathetic activity.

The development of biodegradable materials with controllable degradation properties is beneficial for a variety of applications. Poly(glycerol-sebacate) (PGS) is a promising candidate of biomaterials; so we synthesize a series of poly(glycerol, sebacate, glycolic acid) (PGSG) with 1:2:0, 1:2:0.2, 1:2:0.4, 1:2:0.6, 1:2:1 mole ratio of glycerol, sebacate, and glycolic acid to elucidate the relation of doped glycolic acid to the degradation rate and mechanical properties. The microstructures of the polymers with different doping of glycolic acid were dissimilar. PGSG with glycolic acid in the ratio of 0.2 displayed an integral degree of ordering, different to those with glycolic acid in the ratio of 0, 0.4, 0.6, and 1, which showed mild phase separation structure. The number, DeltaH(m), and temperature of the PGSG melting peaks tended to decrease with the increasing ratio of doped glycolic acid. In vitro and in vivo degradation tests showed that the degradation rate of PGSG with glycolic acid in the ratio of 0.2 was slowest, but in the ratio range of 0, 0.4, and 0.6, the degradation rate increased with the increase of glycolic acid. All PGSG samples displayed good tissue response and anticoagulant effects. Our data suggest that doping glycolic acid can modulate the microstructure and degree of crosslinking of PGS, thereby control the degradation rate of PGS.

Tricarbonyldichlororuthenium (II) dimer (CORM2) has been developed as carbon monoxide (CO) donor. We found that CORM2 activated a type of specific current which was distinct from the big-conductance Ca(2+)-activated K(+) current activated by CO in human umbilical vein endothelial cells (HUVECs). So the aim of the present Study was to characterize the CORM2-induced Current and to access the relation with CO releasing. CORM2 (100 mu M) activated a kind of bi-directional current in HUVECs when the ramp protocol (holding potential 0 mV, from -120 mV to +120 mV) was applied. The Current was not blocked by apamin, TRAM-34 and iberiotoxin, the small, intermediate and big-conductance Ca(2+) -activated K(+) channel blockers, and it was not sensitive to the pipette solution chelated with EGTA. CORM2 still activated the current when the chloride in the pipette Solution was substituted by equal mol gluconic acid. Substitution of the sodium in the bath with choline significantly reduced the current activated by CORM2. The current was regarded as the non-selective cation Current. The current showed slightly inward rectifier property and was not sensitive to Gd(3+) (100 mu M), La(3+) (10 mu M) or 2-aminoethoxydiphenyl borate (100 mu M). CO (10 mu M), CORM3 (100, 200 mu M) and RuCl(3) (100 mu M) were used as controls and showed no effect of the current activation. In conclusion, CORM2 activated the non-selective cation current in HUVECs independently of its CO releasing. (c) 2008 Elsevier B.V. All rights reserved.

Aim To investigate effects of chlorzoxazone on survival and apoptosis of HepG2 cells.Methods The necrosis of HepG2 cells was evaluated by measurement of LDH release.The effects of chlorzoxazone on survival of HepG2 cells were assayed by MTT dyereduction.The effects of chlorzoxazone on cell apoptosis was analyzed by TUNEL method.The ultrastructure of HepG2 cells was observed by transmission electron microscope.Results Chlorzoxazone at concentrations of 100～500 μmol·L-1 inhibited survival ratios of HepG2 cells in a dose-dependent manner significantly.Typical apoptotic changes were observed in HepG2 cells under the fluorescence microscope and transmission electron microscope.Apoptosis of HepG2 cells was induced after treatment of chlorzoxazone at concentrations from 100 μmol·L-1 to 500 μmol·L-1 for 48h,which showed obvious concentration-effect relationship.The apoptotic ratios of HepG2 cells were also increased when chlorzoxazone(100,200,300 and 500 μmol·L-1) was treated for 24,48 and 72 h,which showed obvious time-effect relationship.Conclusion Chlorzoxazone inhibited HepG2 cells survival and induced cell apoptosis.

Aim To approach the antiarrhythmic effects of adenosine and the synergistic antiarrhythmic effects of combination of adenosine and dipyridamole.Methods Different drugs were injected into rats through vena caudalis.The electrocardiogram(ECG)was recorded and analyzed by using BL-420E system.Results Adenosine significantly prolonged the R-R interval in a dose-dependent manner and the effects were enhanced by combination with dipyridamole.Adenosine terminated ventricular arrhythmia induced by adrenalin and BaCl2 in rats and the antiarrhythmic effects were prolonged by combination with dipyridamole.Conclusion Adenosine antagonized the ventricular arrhythmias induced by adrenalin and BaCl2 in rats and the antagonism was enhanced by combination with dipyridamole.