| Backgroud: Recently, our previous research showed that Monocrotaline(MCT)-induced pulmonary arteriolar remodelling was prior to the increase of pulmonaryarterial pressure and the transplanted adipose tissue-derived mesenchymal stem cells(ADMSCs) could significantly attenuate arteriolar remodeling and pulmonary arterialhypertension induced by MCT in rats. However, the effect of ADMSCs on thepulmonary vasomotion function in MCT-treated rats has not been determined.Objective: To investigate the effects of early and delayed intervention of ADMSCson endothelium-dependent relaxation (EDdR), endothelium-independent relaxation(EDiR) and vasoconstrictive function (VCF) in small pulmonary artery (SPA) ringsfrom MCT-induced pulmonary hypertensive rats.Methods: ADMSCs were obtained from subcutaneous adipose tissue of rat，s groin andis isolated by collagenase type I, and infected by Adenoviral vector transfeted withgreen fluorescent protein（GFP）before administration. One hundred and twelve maleSD rats at7-wk-old were randomly assigned into normal control (Ctr), pulmonaryarterial hypertension (PAH), early and delayed intervention of ADMSCs (ADMSCs-EIand ADMSCs-DI) groups. PAH was induced by a dose of40mg/kg MCTintraperitoneally, and Ctr rats were given same volume normal saline.1×106ADMSCswere delivered via left external jugular vein to ADMSCs-EI and ADMSCs-DI groupsrats at1st and2nd wk after administration of MCT respectively, and same volumenormal saline was given in PAH and Ctr groups. At1st,2nd and3rd wk after ADMSCsadministration, mean pulmonary arterial pressure (mPAP) was measured bycatheterization and vasomotion function was gauged by using the method of isolatedvascular ring perfusion to explore the activity of the SPA rings to acetylcholine (Ach),sodium nitroprusside (SNP) and noradrenaline (NE) in every group. The potency ofvascular contraction and relaxation was expressed as the pD2value where pD2is the negative logarithm of the agonist concentration producing50%of the maximumresponse.Results:(1) At1st wk after ADMSCs-EI, mPAP was no statistical difference amongCtr, PAH and ADMSCs-EI groups (P>0.05). At2nd,3rd wk after ADMSCs-EI and1st,2nd,3rd wk after ADMSCs-DI, mPAP in PAH group was significantly increasedcompared with Ctr group and significantly decreased after treatment of ADMSCs(P<0.05, respectively). MPAP at1st,2nd,3rd wk of ADMSCs-EI group respectivelywas lower than1st,2nd,3rd wk of ADMSCs-DI group (P<0.05respectively).(2) At1st,2nd,3rd wk after ADMSCs-EI and ADMSCs-DI, Ach-induced EDdR inPAH group was significantly decreased in SPA rings compared with Ctr group andmarkedly improved after treatment of ADMSCs (P<0.05respectively). EDdR was nostatistical difference among ADMSCs-EI and ADMSCs-DI groups (P>0.05).(3) At1st wk after ADMSCs-EI, SNP-induced EDiR was no statistical differenceamong Ctr, PAH and ADMSCs-EI groups (P>0.05). At2nd,3rd wk after ADMSCs-EIand1st,2nd,3rd wk after ADMSCs-DI, EDiR in PAH group was significantlydecreased in SPA rings compared with Ctr group and markedly improved aftertreatment of ADMSCs (P<0.05respectively). EDiR was no statistical difference amongADMSCs-EI and ADMSCs-DI groups (P>0.05).(4) At1st,2nd,3rd wk after ADMSCs-EI and ADMSCs-DI, there was no statisticaldifference in NE-induced VCF among Ctr, PAH, ADMSCs-EI and ADMSCs-DI groups(P>0.05).Conclusion:(1) The impairment of Ach-induced EDdR in SPA rings fromMCT-treated rats is prior to the increase of pulmonary arterial pressure in the rats. TheDevelopment of MCT-induced pulmonary artery hypertension in rats is associated withimpaired vasodilation in small pulmonary arteries.(2) Whether ADMSCs-EI or ADMSCs-DI, at1st,2nd,3rd after ADMSCsadministration, both significantly restored the impairment of EDdR and EDiR in SPArings and greatly prevents the development of pulmonary arterial hypertension inmonocrotaline-treated rats.(3) The curative effect of ADMSCs-EI group on pulmonary arterial hypertension induced by MCT in rats was better than ADMSCs-DI group. However, there was noobvious difference in the improvement of EDdR and EDiR in SPA rings among twogroups. |
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