Aim: To study the effects of berberine( Ber) on the rapidly activating component( Ⅰ_(Kr)), the slowly activating component(Ⅰ_(Ks)) of the delayed rectifier potassium current and the inward rectifier potassium current(Ⅰ_(K1)) in cardiomyopathic guinea pig ventricular myocytes. Methods: After guinea pigs were ip L-thyroxine 0. 5 mg/kg for 10 d, their hearts were cardiomyopathic. Then whole cell patch-clamp recording technique was used to observe the effect of 30 μmol/L Ber on the Ⅰ_(Kr), Ⅰ_(Ks) and Ⅰ_(K1) in cardiomyopathic guinea pig ventricular myocytes. Results: In cardiomyopathic guinea pig ventricular myocytes, Ber 30 μmol/L markedly inhibited Ⅰ_(Kr) and Ⅰ_(Ks) by 22. 8% and 29. 5% at + 10 mV and + 80 mV, respectively. The effect of Ber on Ⅰ_(Ks) was greater than that on Ⅰ_(Kr). Ber 30 μmol/L also inhibited the inward component of Ⅰ_(K1) by 29. 1% at + 120 mV, but the reverse potential of Ⅰ_(K1) was unaffected. Ber( 1-300 μmol/L) was shown to inhibit Ⅰ_(Kr) and Ⅰ_(Ks) in a concentration-dependent manner. Their IC_(50), were 76. 74 μmol/L and 55. 37 μmol/L, respectively. Conclusion: Ber inhibited Ⅰ_(Kr),Ⅰ_(Ks) and Ⅰ_(K1) in cardiomyopathic guinea pig ventricular myocytes, which may be important in understanding the antiarrhythmic effects of this drug.

AIM: To study the electrical heterogeneity of transient outward potassium current (I_(to)) in left and right ventricular myocytes of cardiomyopathy rat. METHODS: The rats were peritoneally injected with L-thyroxine 0.5 mg/kg for 10 d to establish the model of ventricular hypertrophy. The right and left ventricular parts of the heart were separated and the ventricular myocytes were prepared by step digestion using enzyme solution. I_(to) was recorded by using whole cell patch clamp technique. The change of the electrical heterogeneity was determined. RESULTS: The electrical heterogeneity of I_(to) existed in the normal myocytes of left and right ventricles. In the myocytes of left and right ventricles isolated from the cardiomyopathy rats, the electrical heterogeneity was enhanced obviously and showed statistical difference. At +40 mV depolarizing test potential, the current density of I_(to) in the myocytes of right ventricle was increased from (9.23±0.84) pA/pF to (11.19±1.73) pA/pF, while the current density of I_(to) in the myocytes of left ventricle was decreased from (6.99±1.14) pA/pF to (4.95 ±1.84) pA/pF and the dispersion was increased. The V_(1/2) of right ventricle steady inactivation was increased significantly [from (-68.85±1.37) mV to (-49.86±0.69) mV]. The time constant τ of de-inactivation changed significantly [τ left=(79.16±7.04) ms, τ right=(53.19±3.72) ms]. CONCLUSION: Enhanced electrical heterogeneity of I_(to) in the left and right ventricular myocytes of cardiomyopathy rat may represent one of the important ionic mechanisms for some arrhythmia caused by myocardial hypertrophy.

Objective: To investigate the dynamic expression of placenta growth factor (PlGF) in the lungs and its role in paraquat-induced pulmonary fibrosis and to evaluate the effect of ACEI captopril and AT (1) -receptor blocker losartan on paraquat-induced pulmonary fibrosis. Methods: 84 adult healthy female Sprague-Dawley (SD) rats were randomly divided into four groups of different treatments designated as: Control, PQ alone (PQ) , captopril treatment, losartan treatment. Each group was divided into three subgroups of seven animals each. The animals were killed at either 7, 14 or 28 days after PQ administration. The rats in PQ group, treatment group were treated intragastrically (ig) with PQ (40 mg/kg) and the rats in control group were treated with the same dose of saline at the beginning of the experiment. The treatment group received Captopril (60 mg/kg; ig) or Losartan (10 mg/kg; ig) once a day respectively after PQ administration and the other two groups received saline. At the given timepoint, animals were sacrificed and lungs were harvested. A semiquantitative assay of histological examination, hydroxyproline in lung tissues were used to determine the severity of alveolitis and fibrosis. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of PlGF. Results: Inflammatory cell infiltration and fibrotic scores were more prominent in the model group, hydroxyproline contents in lung tissue were significantly increased after PQ administration compared to the control group. Captopril, losartan apparently attenuated the degree of lung injury and pulmonary fibrosis. On 7th, 14th days, the levels of alveolitis in the intervention groups were significantly alleviated as compared with the model group (P<0.05) . On 28th days, the levels of pulmonary fibrosis in the intervention groups were significantly alleviated as compared with model group (P<0.05) . The hydroxyproline contents in the intervention groups were significantly decreased as compared with model group (P<0.01) . PlGF mRNA on day 7, 14, 28 (1.28±0.29vs0.10±0.01、0.80±0.07vs0.10±0.01、0.65±0.13vs0.10±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF mRNA on day 7, 14, 28 in the captopril and Losartan intervention groups were significantly decreased (0.94±0.04、0.71±0.09、0.52±0.24 and 0.80±0.12、0.66±0.11、0.51±0.03) . PlGF positive expression index on day 7, 14, 28 (2.27±0.34 vs0.13±0.01、1.78±0.41 vs0.14±0.03、1.25±0.69 vs0.13±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF positive expression index on day 7, 14, 28 in the captopril and Losartan treatment groups were significantly decreased (1.53±0.78、1.17±0.79、0.97±0.61 and 1.36±0.63、1.24±0.80、0.83±0.47) . PlGF positive expression index on day 7 in the two intervention groups were significantly decreased, as compared with PQ group (P<0.05) . Conclusion PlGF may plays an important role in the development of pulmonary fibrosis following paraquat-induced lung injury in rats. Captopril and losartan had an inhibitory effect on paraquat-induced pulmonary fibrosis, and the effect may be due to inhibition of angiotensin II and, in part, be associated with reduction in PlGF.