Effects of T-type calcium channel inhibitors on monocrotaline-induced pulmonary arterial hypertension in rats / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the effects of T-type calcium channel inhibitors (ProTx-1,micromolar Ni2+ and Mibefradil) on Monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats.Methods Forty male Sprague-Dawley rats were randomly divided into 5 groupsnormal control group,MCT group,ProTx-1 group,micromolar Ni2+ group and Mibefradil group (8 cases in each group).The right ventricular systolic pressure (RVSP),the right ventricular hypertrophy index (RVHI),and the index of pulmonary vascular remodeling(MA％) were measured on day 28 after MCT-treatment.Western blot was used to detect the expression of proliferating cell nuclear antigen(PCNA) and Cleaved Caspase-3 in pulmonary artery.Results (1)RVSP and RVHI in MCT group were significandy higher than those in the other 4 groups (F =21.55,P ＜ 0.01;F =15.63,P ＜ 0.01).The two indexes in 3 intervention groups were higher than those in normal control group (all P ＜ 0.05),nevertheless,significantly lower than those in MCT group,and 3 intervention groups showed no significant differences (all P ＞ 0.05).(2) MA％ in normal control group [(23.43 ± 1.95) ％] was lower than that in MCT group [(80.42 ± 4.30) ％],ProTx-1 group [(60.35 ± 3.83)％],micromolar Ni2+ group[(62.44 ± 3.81)％] and Mibefradil group[(58.66 ± 4.23)％] (F =216.2,P ＜ 0.01);3 intervention groups showed no significant differences (all P ＞ 0.05),however,they were all significantly lower than that in MCT group.(3) The expression of PCNA in MCT group was higher than that in normal control group,meanwhile,3 intervention groups were significantly lower than that in MCT group.The expression of Cleaved Caspase-3 in MCT group was higher than that in normal control group,nevertheless,3 intervention groups showed no significant changes compared with MCT group,respectively.Conclusions T-type calcium channel inhibitors could ameliorate the progression of MCT-PAH in rats,mainly through suppressing the proliferation of pulmonary artery smooth muscle cells.