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GW24-e1370 Effect of atorvastatin on endothelium-independent relaxation of small Pulmonary arteries in monocrotaline-induced PAH rats
  1. Jiang Zhi1,
  2. Liangdi Xie2
  1. 1First Hospital of Longyan
  2. 2Fujian Hypertension Research Institute, First Affiliated Hospital of Fujian Medical University

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.

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