The Effect And Mechanism Research Of Vardenafil On Moncrotaline-induced Pulmonary Hypertension In Rats

Objectives:To create the model of pulmonary hypertension in rats induced by themonocrotaline, to explore the effect of PDGF in the pathogenesis ofpulmonary hypertension and to observe the effect and possible mechanism ofPDE5inhibitors(vardenafil) to preventive this model of PHAMethods:To create the model of pulmonary hypertension in rats induced by themonocrotaline.30Sprague-Dawley male rats were divided into3groups byrandom[1]: Ⅰblank control group、 Ⅱmodel control group、 Ⅲvardenafilintervention group. In the first day, Ⅰgroup was injected with normal saline2ml/kg,the other2groups were one-time intraperitoneal injected to inducepulmonary arterial hypertension with monocrotaline(MCT55mg/kg).Between the second day to the35thday, Ⅰgroup and Ⅱ group withdistilled water(10ml/kg)to lavage once a day, while groupⅢ withvardenafil(3mg/kg). pay attention to the comparison between groups ofgeneral conditions and weight changes. After3weeks to measure the meanpulmonary artery pressure(mPAP) and the right ventricular pressure(RVP)by using the polygraph system, we measured with a electronic libra to rightventricular hypertrophy index[RV/(LV+S)][2]; HE staining was done asfollows: the percent of wall are（aWA%）=(wall area/total area)×100and thepercent of wall thickness（WT%）=[(medial thickness×2/externaldiameter] ×100. The method of immunohistochemical was assessed the PDGF proteinexpression’s level in pulmonary artery[2].Results:1. Haemodynamics and pulmonary vascular morphology: compared withgroupⅠ, groupⅡ’s mPAP、RVP、RV hypertrophy index expressedsignificant rise, also with arteriole endomembrane, medial thickness, WT%and WA%. compared with groupⅡ, all these indexes in groupⅢ wereobviously dropped,while not reach the level of groupⅠ. Above-mentioneddiversities had statistical significance.2. PDGF-B protein expression in minute pulmonary artery: the expressionof PDGF-B in groupⅡ was hand over fist, groupⅠ was notable reduction,while groupⅢ was between groupⅠ and group Ⅱ. Above-mentioneddiversities had statistical significance.Conclusion:The proliferation of pulmonary VSMC can be induced by MCT[15], thestructure of pulmonary artery remodeled and right ventricularpachynsis,create the model of PHA; Vardenafil could delay the progress ofthis model’s PHA and lighten right ventricular pachynsis. This mechanismsmay be contributed to reduce the expression of PDGF-B protein in smallpulmonary artery.