Study On Interactions Between Captopril And Low-dosage Aspirin And Its Mechanism

Study on interactions between caPtopril and low-dosage aspirinand its mechanismThe combination of caPtopril and low-dosage aspirin are now used extensively incoronary heart disease. The respective beneficial effects of caPtopril and aspirin incoronary heart disease have been well established, but the clinical relevance of the druginteraction between them remains controversial, Which has called into the question ofthe safety of aspirin used in heart falure. TO further evaluate the effects and mechanismof illteractions between these drugs, Author studied the interactions between caPtopriland low-dosage aspirin on phannacodynamics and phimacokinetics. The experimentresults are as fOllows:1' Effccts of interactions between captopril and low-dosage aspirin on experimentalmyocardiaI ischemia in ratsThe myocardial ischemia model induced by isoproterenol was established, theeffects of the combination ofcaPtopril (25. 50. l00mg'kg-' ) and low-dosage aspirin(5mg'kg-' ) on the levels of lactate dehydrogenase (LDH), creatine phosphokinase(CPK) in serum and the changes of myocardial tissue were observed by orthogonaldesign. The results showed that the levels of LDH. CPK in serum and the changes ofmyocardial tissue in model grouP were significanly increased. Neither caPtopril noraspirin was able to reduce the levels of LDH. CPK in serum obviously, but thecombination of captopril and low-dosage aspirin produced significan anagonisticinieractions. Captopril reduced obviously the pathological grades of myocardial tissue,bul aspirin exefted no effect on it. The results suggested that low-dosage aspirin doesnot attenuate the protective effects of caPtOpril on the myocardial tissue injUry, butcaPtopril and low-dosage aspirin combination may produce adversed effects on thelevels of LDH and CPK in serum. 安徽医科大学博士学位论文 2,Effects and mechanism ofinteractlons between caPtoprll and asplnn onm＂red 啊ocardlal cells ofneonate rats The lmured model ofculMedneo咖al ratmyocardlal cells was developed,the activity ofLDH and and the level ofnitric oxide(NO)were measured by LDHklts恤 Gness reagent respectlvelX the 汀山旧cellular free calcium concentrations were measured 0 with Fura－2／pM．The results showedbothc叩toprll and aspirin could reduce the activity ofLDH remarkedly co呷ared withthe model gro叩,especially in lxlo'smol·L"l c叩topril or lxl06mol·LI aspirin,but their combm成ion produced slgnlflc咖 antagonistic Interactions．the level ofNO In medium was significantly Increased atthese optimal doses,but their co毗Inatlon also produced significant antagonistic Interactions． C叩to仰latthe dose oflxlo"smol·LI reduced obviouslythe Intracellularfree calcium concentrations In lmmed model,b山 aspirin(lxl06mol·LI)alo忧 or in combination with captopril(lxlo'mol·L')signific咖ly Increased It．The resuits suggested that 雪 Captopfll nd ISplflll COffiblflatl。11 pf。dllCCd SlglllfiCmt gntsg。IllstlC llltCfs。ti。ifs。11 lq＂red myocardlal cells from neonate rats,and What's more,the effects m缈b related to its actions ofreducing the production ofNO and Increasing the皿acellular free calcium concentrations． 3,Effects ofcaPtoprll and low－dosage aspirin combination on leftventrlcular remodeling and c－fos protein expression Inhe咖 failure rats WfliTIcular remodeling曲er acme myocardlal In趾ctlon Is a precursor of＊thesor develoPment ofovert he?failure and Is an imPort咖 Predlctor ofmoMlity．Left ventricular hvnertronhv(LV0)nd mvoca fdfdlal llbrosls(M厂)re t WOWO malor ra山ciogIcal factors ofleft ventrlcular remodeling(wR)．Acute myocardial in初ction(AMI)and chniche叫 failure(CHF)rats sl...