Maisel A S, Phillips C, Michel M C, Ziegler M G, Carter S M
Department of Medicine, University of California, San Diego, La Jolla.
Circulation. 1989 Sep;80(3):669-75. doi: 10.1161/01.cir.80.3.669.
The interaction of the renin-angiotensin system and the sympathetic nervous system in patients with congestive heart failure is not well understood. We tested the hypothesis that angiotensin-converting enzyme inhibitors can resensitize the beta-adrenergic receptor system. Guinea pigs were given captopril, isoproterenol, or both for 2 weeks. At death, cardiac sarcolemmal and light vesicle fractions and intact mononuclear leukocytes were prepared. Captopril treatment led to an up-regulation of cardiac beta 1- but not mononuclear leukocyte beta 2-adrenergic receptors and an increase in isoproterenol-stimulated adenylate cyclase activity in the heart. Animals treated with isoproterenol developed cardiac hypertrophy, had increased plasma norepinephrine levels, and had a decreased number and responsiveness of both cardiac and mononuclear leukocyte beta-adrenergic receptors. Concomitant treatment with captopril attenuated alterations of heart weight, plasma norepinephrine levels, and cardiac beta-receptor density and function. In contrast to its cardiac effects, captopril treatment did not diminish the down-regulation of mononuclear leukocyte beta 2-adrenergic receptors by isoproterenol. Our data suggest that captopril may resensitize the cardiac but not the mononuclear leukocyte beta-adrenergic receptor-adenylate cyclase system after long-term catecholamine exposure.
充血性心力衰竭患者体内肾素 - 血管紧张素系统与交感神经系统之间的相互作用尚未完全明确。我们检验了血管紧张素转换酶抑制剂可使β - 肾上腺素能受体系统重新敏感化的假说。给豚鼠服用卡托普利、异丙肾上腺素或两者同时服用两周。在处死时，制备心脏肌膜和轻囊泡部分以及完整的单核白细胞。卡托普利治疗导致心脏β1 - 肾上腺素能受体上调，但单核白细胞β2 - 肾上腺素能受体未上调，且心脏中异丙肾上腺素刺激的腺苷酸环化酶活性增加。用异丙肾上腺素治疗的动物出现心脏肥大，血浆去甲肾上腺素水平升高，心脏和单核白细胞β - 肾上腺素能受体的数量和反应性均降低。卡托普利与异丙肾上腺素同时治疗可减轻心脏重量、血浆去甲肾上腺素水平以及心脏β受体密度和功能的改变。与对心脏的作用相反，卡托普利治疗并未减弱异丙肾上腺素对单核白细胞β2 - 肾上腺素能受体的下调作用。我们的数据表明，长期接触儿茶酚胺后，卡托普利可能使心脏β - 肾上腺素能受体 - 腺苷酸环化酶系统重新敏感化，但不能使单核白细胞的该系统重新敏感化。
