EFFECTS OF DILTIAZEM AND BENAZEPRIL ON MONOCROTALINE-INDUCED PULMONARY ARTERIAL REMODELING IN RATS: PP.29.146

Abstract

Introduction: To evaluate the effects of diltiazem and benazepril on monocrotaline-induced pulmonary arterial remodeling in rats. Methods: Forty Sprague-Dawley rats were randomly assigned into four groups: normal control (Ctr), pulmonary arterial hypertension (PAH), diltiazem (Dil) and benazepril treated group(Ben). The rats were given a dose of 40 mg/Kg monocrotaline intraperitoneally in PAH, diltiazem and benazepril treated groups and untreated rats were given 1 ml NS intraperitoneally as control. After 4 weeks, the rats were given 25 mg/Kg/d of diltiazem and 10 mg/Kg/d of benazepril by gavage respectively in diltiazem and benazepril treated groups for 4 weeks. 4 weeks after medication, mean of pulmonary arterial pressure(MPAP) and right ventricular hypertrophy index (RVHI) were measured, and WT% and WA% of pulmonary arterioles were evaluated. The protein analysis for Cav1c, SERCA-2a, IP3R-1 and RyR-3 in pulmonary artery was evaluated by Western-Blot. Results: MPAP and RVHI were significantly increased in PAH. MPAP and RVHI were significantly decreased after diltiazem and benazepril treatment(P < 0.05 respectively). Compared with Ctr group, WT% and WA% were significantly increased in PAH. Administration of diltiazem and benazepril, WT% and WA% were significantly reduced.[MPAP: Ctr(23.22+/−3.27), PAH(36.12+/−4.17), Dil(25.27+/−6.18) vs Ben(28.11+/−6.02)mmHg; RVHI: Ctr(25.58+/−2.94), PAH(45.60+/−3.81), Dil(39.96+/−2.61) vs Ben(39.50+/−4.90)%; WT: Ctr(37.63+/−3.63), PAH(58.48+/−4.59), Dil(43.04+/−4.96) vs Ben(37.41+/−4.35)%; WA: Ctr(51.37+/−6.40), PAH(76.84+/−7.04), Dil(61.74+/−4.90) vs Ben(53.86+/−5.53)%, P < 0.05 respectively] Cav1c and RyR-3 expression was significantly downregulated after diltiazem and benazepril treatment(P < 0.05 respectively). And RyR-3 expression in benazepril treated group was less than that in diltiazem treated group (P < 0.05). There were no significant differences in the expression of SERCA-2a between diltiazem and benazepril treated groups and PAH(P > 0.05 respectively). As to IP3R-1, diltiazem and benazepril treated groups also showed downregulated expression compared with PAH(P < 0.05 respectively). Conclusion: Diltiazem, as effective as benazepril, could reduce pulmonary arterial pressure, attenuate right ventricular hypertrophy and pulmonary arterioles remodeling and regulate calcium channels expression in pulmonary artery in monocrotaline-induced pulmonary arterial hypertensive rats.