Forster C, Naik G O, Larosa G
Department of Medicine, University of Toronto, St. Michael's Hospital, ON, Canada.
Can J Physiol Pharmacol. 1994 Jun;72(6):667-72. doi: 10.1139/y94-094.
In heart failure, both the sympathetic nervous system and the renin angiotensin system play important pathophysiological roles, and the two systems may interact with each other, e.g., angiotensin II facilitating noradrenaline release. An abnormality in beta-adrenoceptor density (i.e., a decrease) occurs in clinical and pacing-induced heart failure. This observation together with the therapeutic effectiveness of converting-enzyme inhibitors in the management of patients with heart failure led to the current investigation. The aim was to explore the impact of chronic enalapril treatment on the status of myocardial beta-adrenoceptors in dogs paced (250 beats.min-1) to end-stage heart failure. Placebo or enalapril treatment (5 mg b.i.d.) commenced 1 week after the onset of ventricular pacing and continued until end-stage heart failure was reached. Myocardial beta-adrenoceptor density and affinity were assessed by radioligand binding with [125I]iodocyanopindolol. Left ventricular angiotensin II formation and noradrenaline concentration were measured. In addition, plasma renin activity and plasma noradrenaline levels were determined. The results showed that there was a significant increase in beta-adrenoceptor density following enalapril treatment compared with placebo in the heart-failure group. Enalapril did not change the beta-adrenoceptor density in the control animals. However, in both heart failure and control animals, enalapril caused an unexpected increase in Kd. Furthermore, in heart failure, enalapril caused a significant increase in myocardial angiotensin II formation. We conclude that enalapril prevents or reverses the myocardial beta-adrenoceptor abnormality seen in heart failure and promotes angiotensin II formation.
在心力衰竭中，交感神经系统和肾素血管紧张素系统均发挥重要的病理生理作用，且这两个系统可能相互作用，例如血管紧张素II促进去甲肾上腺素释放。在临床和起搏诱导的心力衰竭中会出现β-肾上腺素能受体密度异常（即降低）。这一观察结果以及血管紧张素转换酶抑制剂在心力衰竭患者治疗中的有效性引发了当前的研究。目的是探讨慢性依那普利治疗对起搏（250次/分钟）至终末期心力衰竭犬心肌β-肾上腺素能受体状态的影响。在心室起搏开始1周后开始给予安慰剂或依那普利治疗（5mg，每日两次），并持续至达到终末期心力衰竭。通过与[125I]碘氰吲哚洛尔进行放射性配体结合来评估心肌β-肾上腺素能受体密度和亲和力。测量左心室血管紧张素II的生成和去甲肾上腺素浓度。此外，还测定了血浆肾素活性和血浆去甲肾上腺素水平。结果显示，与心力衰竭组给予安慰剂相比，依那普利治疗后β-肾上腺素能受体密度显著增加。依那普利对对照动物的β-肾上腺素能受体密度无影响。然而，在心力衰竭和对照动物中，依那普利均导致解离常数意外升高。此外，在心力衰竭中，依那普利导致心肌血管紧张素II生成显著增加。我们得出结论，依那普利可预防或逆转心力衰竭中出现的心肌β-肾上腺素能受体异常，并促进血管紧张素II生成。
