| Objective Treatment with β blockers reduce mortality and sudden death among patients with myocardial infarction,and it has been proved thatβ blockers have great clinic efficacy given after myocardial infarction.However,the mechanisms of their actions have not been elucidated completely, including the one by which β blockers can improve cardiac function. In this research, we investigated changes of nitric oxide and CGRP in plasma during bisoprolol's improving left ventricular function after experimented myocardial infarction and effects of bisoprolol on ntric oxide production in cultured myocardial cells pretreated with IL-1β in order to make it clear what roles iNOS/NO and CGRP play during β blockers' improving cardiac function after myocardial infarction.Methods (1) Myocardial infarction model was created in rabbits by ligating coronary artery.After the operation,rabbits were randomly divided into 3 groups:sham-operated group(S group),myocardial-infarction group(M group) and bisoprolol-treated group(B group). (2) 3 months after the operation, hymodynamics were measured using invasive methods.including heart rate,LVEDP and 眒ax-LV dp/dt. (3) Blood samples were obtained from left ventricles.then NO and CGRP in plasma were measured by Griess method orimmunoreactivitic method. ( 4 ) Cardiac cells were prepared from Sprague-Dawley rats,and effects of bisoprolol on nitric oxide synthase in the myocytes were investigated with or without IL-1 3 in the condition of normoxia or hypoxia.Results (1)3 weeks after therapy,bisoprolol improved cardiac function in rabbites with myocardial infarction,especially ?max-LV dp/dt (all P < 0.01) .meanwhile there was a trend that LVEDP tended to be decreased by bisoprolol in spite that the difference was not significant (P=0.063) .(2)3 weeks after operation,plasma NO in M group increased significantly conpared to S group (P<0.01) ;while bisoprolol had no effect on NO production (Vs M group, P=0.081;Vs S group,P<0.01) .(3)Plasma CGRP in M group increased significantly compared to S group (P<0.01) ;bisoprolol reduced CGRP production(Vs M group,P<0.01; Vs S group, P=0.939).(4)50umol/L bisoprolol had no effects on NO production in the myocytes (P=0.533) .Treated with 10 ng/ml Eft IL-1 3 for 48 hours,NO production increased significantly (P<0.01) . lfimol/L bisoprolo had no effects on NO production compared to control group (IL-1 & group) (P=0.156) . However 50umol/L or 500u.mol/L bisoprolol decreased NO production(all P<0.01) ,and there no significant difference between the two groups (P=0.903 ) .Hypoxia for 48 hours had no effects on NO production withou IL-1 3 (P=0.381) ,but it reduced IL-1 3 梚nduced NO production in myocytes (P<0.01) ,When hypoxia existed,50umol/L bisoprolol enhanced the reduce of NO production induced by IL-1 3 .Conclusion 3 weeks' therapy with bisoprolol improved rabbites' cardiac function after experimented myocardial infarction,whilie it didn't reduce NO production. To increase the release of CGRP is one of mechaisms by which body can compensate the deterioration of hymodynamics. Beta blockers can influenc CGRP release by alteration of hymodynamics,then the increased CGRP improved cardiac function,and in the reverse way ameliorated cardiac function decreased release of CGRP. When dysfunction occurred, expression of iNOS increases,and NO from iNOS inhibites myocardial constractility. We found that bisoprolol can reduce NO production in myocytes induced by cytokines.so NO/iNOS and CGRP do play important roles in the process by which 3 blockers improve cardiac function after myocardial infarction.In summary,iNOS/NO and CGRP do play roles in the process by which & blockers improve cardiac function after myocardial infarction.Thus,we clarited another mechanism by which ? blockers benefit patients with myocardial infarction.lt needs more research to make it clear by which ways 3 blockers can influnce CGRP in vivo and iNOS/NO in vitro.
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