Effect Of Angiotensin Ⅱ And Aldosterone On Airway Remodeling In Asthmatic Mice

Airway remodeling, an important feature of asthma, is characterized by structural changes in the bronchial walls that mainly include airway wall thickening, airway wall fibrosis, smooth muscle cells hypertrophy and hyperplasia. AngiotensinⅡ(ATⅡ) and aldosterone(ALD) are two important components of renin-angiotensin-aldosterone system (RAAS). It was showed recently that local RAAS was found in many organs such as cardiac ventricle, blood vessel and kidney, and both ATⅡand ALD may be actively involved in these organic remodeling. It was reported there was local RAAS in lung tissue and lung fibrosis could be relieved even reversed when RASS was inhibited. Other investigations showed that plasma levels of ATⅡand ALD were elevated in asthma. All these investigations indicate ATⅡand ALD may be involved in airway remodeling when asthma occurred.In order to explore the role of ATⅡand ALD in airway remodeling in asthma, asthmatic model were established by ovalbumin (OVA) peritoneal injection and inhalation. ATⅡand ALD were assayed in lung tissue by radioimmunoassay. Captopril and spironolactone were used to investigate its effects on airway remodeling and transforming growth factor-β1 (TGF-β1)mRNA expression. Thus, BALB/c mice were randomly divided into 5 groups: control group (group A), asthmatic model group (group B), captopril group (group C), spironolactone group (group D), and combination of captopril and spironolactone group (group E) with n=10 in each group. The latter four groups were established by ovalbumin and group A was given saline as control. Group C,D and E were administered captopril, spironolactone, the combination of captopril and spironolactone intragastrically for 8 weeks respectively after the establishment of asthmatic models. Group A and B were give water as control. Mice in all groups were sacrificed at the end of specified follow-up period and the lung tissue was harvested. The concentrations of ATⅡand ALD in lung tissue were detected by radioimmunoassay. Morphological changes were observed by tissue staining Thickness and perimeter of airway wall were examined by image analysis system for the percentage of thickness. The expression of TGF-β1 mRNA in lung tissue was assessed by semi-quantitative reverse transcription polymerase chain reaction.The results show that:①The contents of ATⅡand ALD in lung tissue were higher significantly in group B than that of group A (P<0.01). But the content of ATⅡwas decreased significantly after captopril treatment (P<0.01) and the content of ALD in lung tissue was also decreased significantly in group D after spironolactone treatment (P<0.01), which were lower than those in group B. The ATⅡand ALD contents of lung tissue in group E were lower than than those in group C and D (P<0.05);②The airway wall in group B revealed remarkable morphological changes of airway remodeling: airway smooth muscle hyperthrophy/hyperplasy, mass infiltration of eosinophil in airway wall or its vicinity, and airway wall was thicker in group B than that in group A (P<0.01),But above changes were relieved in group C and D after captopril or spironolactone therapy: The airway wall was thinner significantly in group C and D than that in group B (P<0.01). There was few eosinophil in airway walls of group E, and the airway wall was even thinner in group E than ether in group C or group D after captopril and spironolactone were treated simultaneously (P<0.05);③Among the five groups, the TGF-β1 mRNA expression in lung tissue was highest in group B(P<0.01), but it was attenuated after captopril or spironolactone treatment(P<0.01): the TGF-β1 mRNA expression was lower in group C, D and E than that in group B (P<0.01), and it was even lower in group E than that in group C or group D after the allied therapy of captopril and spironolactone (P<0.01).Taken together, these results suggest that ATⅡand ALD may be involved in airway remodeling. Captopril and spironolactone may have synergistic inhibitory effects on airway remodeling in asthmatic mice and its mechanism may be associated with the down-regulation of TGF-β1 mRNA expression in lung tissue, which provides new insight to the treatment of airway remodeling in asthma.