The Expression Of Angiotensinâ…¡ Receptor And β₂-adrenergic Receptor In The Lung Of Asthmatic Rat And Their Regulation By Valsartan

Background:Asthma is one of the high morbidity and mortality rate diseases over the world,aeroallergen,airway inflammation,high airway reactive,nervous factors and their interaction are highly related with the progress of asthma.As receptors,they are many research onβ₂-AR,M receptor,glucocorticoid receptor,which play an important part in the morbidity and treat of asthma.Recent research indicate that the incereased Angâ…¡can be found in the peripheral blood of asthmatic patients.The antagon of AT₁R have the action of decrease the cell number in bronchoal veolar lavage fluid(BALF)and relieve airway reactive.Moreover,the antagon of AT₁R can improve airway inflammation and relieve airway resistance,which suggests Angâ…¡and its receptors participate the progress of asthma.However,there is few report about the expression of ATR,how ATR interaction with other receptors in the lung. By intervention on asthmatic rat samples with valsartan,this article is designed to study the expression ATR andβ₂-AR,also the action and mechanism of Angâ…¡and its receptors in the chronic asthma.Objective:To investigate the expression of angiotensinâ…¡receptor subtypes (AT₁R,AT₂R)andβ₂- adrenergic receptor(AR)in the lungs of asthmatic rats, and the influence of valsartan upon their expression.Methods:Fifty Wistar rats were randomly divided into 5 groups,group A (control),group B(asthma),group C₁(Valsartan 15mg/kg),group C₂ (Valsartan 30mg/kg),group C₃(Valsartan 50mg/kg),each containing 10 subjects.The rats were sensitized by 10%ovalbumin peritoneal injection and challenged by 1%ovalbumin aerosol inhalation to establish the asthmatic model.The levels of AT₁R,AT₂R andβ₂-AR mRNA and protein in lung tissues were analyzed by reverse transcriptase-polymerase chain reaction(RT-PCR) and Western blot.Results:â‘ Comparing with control(group A),the expression levels of AT₁R in asthmatic subjects(group B)was significantly increased(P＜0.05). Valsartan decreased the level of AT₁R in asthmatic groups(group C₁,C₂ and C₃).A negative correlation between the expression of AT₁R and the dose of valsartan was demonstrated(r=-0.96).â‘¡There was no AT₂R expression in control(group A),while in asthmatic subjects(group B)the AT₂R expression increased markably.By the use of valsartan,the elevated level of AT₂R either could not be found(group C₁)or markedly decreased(group C₂ and C₃);â‘¢Comparing with control(group A),theβ₂-AR level in asthmatic subjects (group B)was significantly decreased(P＜0.01).By the use of valsartan,the positive expression rate ofβ₂-AR increased in group C₁,C₂ and C₃ compared with group B(P＜0.05,respectively);â‘£Comparing with control(group A),the expression levels of STAT3 in asthmatic subjects(group B)was significantly increased(P＜0.05).Valsartan decreased the level of STAT3 in asthmatic groups(group C₁,C₂ and C₃).Conclusions:The results suggest that angiotensinâ…¡receptors(ATR)are expressed in rat lung tissues.The ATR may be activated and play a role in asthma attack.The expression and the function of ATR in the asthmatic rats lung may be related with the change ofβ₂-AR.The expression of AT₁R and AT₂R in the asthmatic rats lung were increased,whileβ₂-AR decreased. Valsartan can inhibit the expression of AT₁R and restore the expression ofβ₂-AR.One possible pathogenes of Angâ…¡is by STAT3 pathway.