The Effect Of Atorvastatin On Vasodilatation Function In The Pulmonary Arteries In Monocrotaline-induced PAH Rats

Objective: To examine the effects of different doses of atorvastatin preventivetreatment on the vasodilatation of middle and small pulmonary artery rings inmonocrotaline（MCT）-induced pulmonary hypertensive（PAH） rats.Methods:72Male SD rats were randomly assigned into: normal control （Ctr）, PAH,PAH pretreated with low dose of (L_Ator) and high dose of (H_Ator) atorvastatin （Ator）respectively. PAH was induced by single MCT intraperitoneal （i.p.） injection at adose of40mg/kg. Drug was given by gavage. Rats were sacrified1,2and4weeksafter drug administration. Mean pulmonary artery pressure （mPAP）, right ventricularhypertrophy index（RVHI%）, acetylcholine（Ach）-induced endothelium-dependentrelaxation （EDdR） and sodium nitroprusside（SNP）-induced endothelium-independentrelaxation（EDiR） were determined. The potency of vascular relaxation was expressedas the pD2.Results: mPAP was significantly higher in PAH rats than that in Ctr4weeks afterMCT injection（PAH:32.19±0.91vs Ctr:14.39±0.35, p<0.01）. Pretreated with Ator for4weeks, mPAP was significantly decreased both in L_Atorand in H_Atorrats as comparedwith PAH rats(L_Ator:19.13±1.01, H_Ator:17.55±0.20vs PAH:32.19±0.91; p <0.01).RVHI%significantly increased in PAH rats4weeks after MCT i.p.（PAH:56.76±5.86vs Ctr:21.57±2.99, p <0.01）.However, it was significantlydecreased4weeks after pretreated with Ator in L_Atorand H_Atorrats compared withPAH(L_Ator:36.09±4.29vs PAH:56.76±5.86,P<0.01; H_Ator:28.93±5.08vsPAH:56.76±5.86, p<0.01). Ach-induced EDdR of SPA rings in PAH was notsignificantly decreased1week after MCT injection, but markedly decreased2weeksafter MCT injection（PAH:5.81±0.87vs Ctr:8.33±0.86, p<0.01）.While Ach-inducedEDdR was significantly decreased in both L_Atorand H_Atorrats4weeks after the pretreatment (L_Ator:6.51±0.99，H_Ator:6.41±0.56vs Ctr:8.33±0.86, p <0.05), but not in1and2weeks. SNP-induced EDiR of SPA rings in PAH was not significantly decreased1or2weeks after MCT injection, but it was significantly decreased4weeks after theinjection （5.89±0.97vs8.53±0.91, p<0.01）.There were no difference in EDiR of SPArings among Ctr, L_Atorand H_Atorrats1week after pretreated with different doses ofAtor. However, Snp-induced EDiR was significantly ameliorated in SPA rings2weeks after the treatment in H_Atorrats compared with Ctr rats （9.93±0.78vs8.53±0.91,p<0.01）. Snp-induced EDiR was decreased both in L_Atorand H_Atorrats4weeks after the preventive treatment （6.81±0.76,6.92±0.62vs8.53±0.91, p<0.05）.Similar results were observed in isolated MPA rings.Conclusion:Early preventive treatment with low dose of atorvastatin has protectiveeffects on the early damage of endothelium-dependent vasodilatation function insmall and middle pulmonary artery of MCT-induced PAH rats. Both high and lowdose of atorvastatin show preventive effects on EDiR in SPA, but early protectiveeffect was only shown in high dose.