Article Text
Abstract
Objectives To examine the preventive effect of atorvastatin on sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EDiR) in small pulmonary artery (SPA) rings in monocrotaline (MCT)-induced pulmonary hypertension rats.
Methods 72 Male SD rats were randomly assigned into four groups: normal control (Ctr), pulmonary arterial hypertension (PAH), PAH preventively treated with 5 mg/kg/d (Lator) and 10 mg/kg/d (Hator) atorvastatin respectively. Rats were sacrified at the end of 1st, 2nd and 4th wks after drug gavage. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI%), and vasomotion function were determined. The potency of vascular relaxation was expressed as the pD2 value.
Results mPAP in PAH was significantly higher than that in Ctr 4 wks after monocrotaline (MCT) injection (32.19 ± 0.91 vs 14.39 ± 0.35, p < 0.01). While preventively treated with atorvastatin for 4 wks, mPAP was significantly decreased in Lator and Hator group as compared with PAH(19.13 ± 1.01, 17.55 ± 0.20 vs 32.19 ± 0.91; p < 0.01). RVHI% was significantly decreased 4 wks after preventively treated with atorvastatin in Lator and Hator rats compared with PAH(36.09 ± 4.29 vs 56.76 ± 5.86; 28.93 ± 5.08 vs 56.76 ± 5.86, p < 0.01). SNP-induced EDiR of SPA rings in PAH was not significantly decreased 1 or 2 wks after MCT injection, while it was significantly decreased 4 wks after the injection (5.89 ± 0.97 vs 8.53 ± 0.91, p < 0.01). There were no difference in Snp-induced EDiR of SPA rings among Ctr, Lator and Hator rats 1 week after preventively treated with different doses of atorvastatin. However, 2 weeks after the treatment, the Snp-induced EDiR was only significantly improved in SPA rings in Hator rats compared with Ctr rats (9.93 ± 0.78 vs 8.53 ± 0.91, p < 0.01). While the Snp-induced EDiR was decreased in both Lator and Hator rats 4 weeks after the preventive treatment (6.81 ± 0.76,6.92 ± 0.62 vs8.53 ± 0.91, p < 0.05).
Conclusions Early preventive treatment with high dose of atorvastatin has protective effects on the early damage of endothelium-independent vasodilatation function in small pulmonary artery of MCT-induced PAH rats.