| Objectives: To investigate the effects of atorvastatin on pulmonary arterial hypertension induced by twice intraperitoneal injection of monocrotaline at a dose of 20mg/kg.Methods: Ninety-six male adult Sprague-Dawley rats were randomized into three groups: control,pulmonary arterial hypertension and atorvastatin group.A rat pulmonary arterial hypertension model was established by twice intraperitoneal injection of monocrotaline at a dose of 20mg/kg respectively at the 1st day and 8th day.At the same time of first injection of monocrotaline,rats in atorvastain group received 10mg/?kg·d?atorvastatin by gavage.Mean pulmonary arterial blood pressure?m PAP?was measured by right heart catheterization,right ventricular hypertrophy index?RVHI?was calculated by weighting method,ratio of wall/lumen thickness?WT%?and ratio of wall/lumen area?WA%?were calculated by graphical analysis,and endothelium-dependent relaxations?EDd Rs?,endothelium-independent relaxations?EDi Rs?,as well as vascular construction function?VCF?were determined by multi wire myograph system respectively at the end of 2nd and 4th week after monocrotaline injection.Results:1.At the end of 2nd week after monocrotaline injection,there were no significant changes of m PAP and RVHI among three groups.However,at the end of 4th week,compared with control group,both m PAP and RVHI were dramatically increased in pulmonary arterial hypertension group [m PAP:?33.55±3.47???25.46±4.04?versus?18.91±2.13?mm Hg;RVHI:?45.10±9.67???35.24±5.89?versus?21.84±5.02?% ],while compared with pulmonary arterial hypertension group,either m PAP or RVHI in atorvastain group was decreased which was still higher than that of control group?P<0.05?.2.No matter at the end of 2nd or 4th week after monocrotaline injection,both WT% and WA% were significantly increased in pulmonary arterial hypertension group compared with control group [end of 2nd week——WT%:?42.17±4.12???33.83±1.23?versus?28.95±2.97?,WA%:?65.91±4.92???58.37±3.42?versus?49.08±2.84?;end of 4th week——WT%:?55.79±4.15???40.69±2.53?versus?29.38±4.50?;WA%:?79.75±3.30???64.11±3.18?vs?49.44±6.28?],however,either WT% or WA% in atorvastain group was lower than that of pulmonary arterial hypertension group but higher than that of control group?all P<0.05?.3.No matter at the end of 2nd or 4th week after monocrotaline injection,compared with control group,not only EDd Rs but also EDi Rs of small pulmonary arteries were remarkably impaired in pulmonary arterial hypertension group [p D2:end of 2nd week——EDd Rs:?4.91±0.42???6.06±1.30?versus?7.48±0.40?,EDi Rs:?6.36±0.24???7.56±0.57?versus?8.13±0.46?;end of 4th week——EDd Rs:?3.95±1.29???5.24±0.67?versus?7.12±0.89?,EDi Rs:p D2:?5.93±0.30???7.14±0.36?versus?8.03±0.32?],while those in atorvastain group were improved compared with pulmonary arterial hypertension group which were still impaired compared with control group?all P<0.05?.However,at the end of 2nd and 4th week,neither control,pulmonary arterial hypertension nor artovastatin group's VCF turned out to be with significant difference?all P>0.05?.Conclusion: Twice intraperitoneal injection of monocrotaline at a dose of 20mg/kg may establish a stable pulmonary arterial hypertension.Atorvastatin significantly attenuated monocrotaline-induced pulmonary arterial hypertension by ameliorating pulmonary vascular remodeling and improving pulmonary vascular relaxation. |
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