Objectives To examine the preventive effect of atorvastatin on acetylcholine (Ach)-induced endothelium-dependentrelaxation (EDdR) in small pulmonary artery (SPA) rings in monocrotaline (MCT)-inducedpulmonary hypertension rats.
Methods 72 MaleSD rats were randomly assigned into four groups: normal control (Ctr), pulmonaryarterial hypertension (PAH), PAH preventively treated with 5 mg/kg/d (Lator)and 10 mg/kg/d (Hator) atorvastatin respectively. Rats were sacrifiedat the end of 1st, 2nd and 4th wks after administration. Mean pulmonary arterypressure (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 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 decreasedin Lator andHator group as compared with PAH group (19.13 ± 1.01, 17.55 ± 0.20vs 32.19 ± 0.91; p <0.01). RVHI% was significantly decreased after 4 wks preventively treated with atorvastatin in Lator and Hator group compared with PAH group (36.09 ± 4.29 vs 56.76 ± 5.86; 28.93 ± 5.08 vs 56.76 ± 5.86, p < 0.01). Ach-induced EDdR of SPA rings in PAH was not significantly decreased 1 week afterMCT injection, yet markedly decreased 2 weeks after MCT injection (5.81 ± 0.87 vs 8.33 ± 0.86, p < 0.01). There were no differences in Ach-induced EDdRin SPA rings among Ctr, Lator and Hator rats after 1 week or 2 wks preventively treated with different doses of atorvastatin. However, Ach-inducedEDdR in Lator and Hator rats was decreased 4 wks after the preventive treatment (6.51 ± 0.99, 6.41 ± 0.56vs 8.33 ± 0.86, p <0.05).
Conclusions Earlypreventive treatment with low dose of atorvastatin has protective effects onthe early damage of endothelium-dependent vasodilatation function in smallpulmonary artery of MCT-induced PAH rats.