REDUCTION OF BETA-ADRENOCEPTOR FUNCTION BY OXIDATIVE STRESS IN THE HEART
REDUCTION OF BETA-ADRENOCEPTOR FUNCTION BY OXIDATIVE STRESS IN THE HEART
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DOI：
10.1016/0891-5849(90)90002-z
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发表时间：
1990-01-01
影响因子：
7.4
通讯作者：
BAST, A
中科院分区：
文献类型：
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作者：
HAENEN, GRMM;VEERMAN, M;BAST, A
测定氧化应激对心脏β-肾上腺素能受体功能的影响。为此，用0.1 mM过氧化氢异丙苯染毒大鼠左心房和右心室条20分钟。结果发现，氧化应激使脑室膜β-肾上腺素能受体数目增加，c-AMP生成减少。在大鼠左心房和大鼠右室条上，β-肾上腺素能受体激动剂的作用约为对照组的30%，而β-肾上腺素能受体介导的最大反应则减少到50%。使用来自对照心房和暴露于氧化应激的心房的膜，发现氧化应激对β-肾上腺素受体密度没有影响，也不影响(-)异丙肾上腺素对该受体的亲和力。暴露于氧化应激下的心房膜中c-AMP的产量减少到对照心房膜中c-AMP产量的30%左右。此外，研究发现，将受体激活产生的刺激转化为效应的功能的形状不会因氧化应激而改变。结论：氧化应激降低β-肾上腺素能受体激动剂的药效可能是由于c-AMP生成减少所致。由于Forsklin和二丁酰c-AMP的疗效不受氧化应激的影响，c-AMP的形成减少可能是由于受体和腺苷环化酶之间的偶联受损所致。β-肾上腺素受体介导的最大反应的减少可能是氧化应激过程中产生的细胞毒性醛的结果。在缺血时，儿茶酚胺的释放和随后的β-肾上腺素能受体的过度刺激会导致心脏毒性。本研究表明，氧化应激可降低β-肾上腺素能受体功能。这可能代表了一种保护性的生理反馈机制，保护心脏免受过度的β-肾上腺素受体刺激。
The effect of oxidative stress on .beta.-adrenoceptor function in the heart was determined. To this end ventricle membranes, field-stimulated rat left atria and field-stimulated rat right ventricle strips were exposed to 0.1 mM cumene hydroperoxide for 20 min. It was found that oxidative stress increased .beta.-adrenoceptor number and reduced c-AMP formation in the ventricle membranes. In the rat left atria and rat right ventricle strips the efficacy of .beta.-adrenoceptor agonists was reduced to approximately 30% of the control value, whereas maximal .beta.-adrenoceptor-mediated response was reduced to 50%. Using membranes from control atria and from atria exposed to oxidative stress, it was found that oxidative stress had no effect on .beta.-adrenoceptor density, nor on the affinity of (-)isoproterenol for the receptor. c-AMP production in membranes prepared from atria exposed to oxidative stress was reduced to approximately 30% of the c-AMP production in membranes prepared of control atria. In addition, it was found that the shape of the function that transduces the stimulus which is generated by receptor activation into an effect, is not altered by oxidative stress. It was concluded that the reduction of the efficacy of .beta.-adrenoceptor agonists by oxidative stress is probably caused by the reduction of c-AMP formation. Because the efficacy of forskolin and of dibutyryl c-AMP was not affected by oxidative stress, the reduced c-AMP formation is probably caused by an impaired coupling between the receptor and adenylate cyclase. The reduction of maximal .beta.-adrenoceptor-mediated response might be the result of cytotoxic aldehydes that are produced during oxidative stress. In ischemia, catecholamine release and subsequent .beta.-adrenoceptor hyperstimulation lead to cardiotoxicity. As shown in the present study, oxidative stress reduces .beta.-adrenoceptor function. This might represent a protective physiological feedback mechanism that protects the heart against excessive .beta.-adrenoceptor stimulation.