Larosa G, Forster C
Department of Pharmacology, University of Toronto, Canada.
J Vasc Res. 1996 Jan-Feb;33(1):62-70. doi: 10.1159/000159133.
Congestive heart failure is associated with abnormalities in myocardial beta-adrenoceptor function. The extent of vascular beta-adrenoceptor alterations at heart failure, however, is unknown. Accordingly, we examined beta-adrenoceptor-mediated relaxations in both circumflex (CRX) and left anterior descending (LAD) coronary arteries with and without endothelium from dogs in early and end-stage heart failure induced by rapid ventricular pacing (1 and 4 weeks pacing at 250 beats x min-1, respectively). At early heart failure, (1) CRX with endothelium were more sensitive to isoproterenol than CRX without endothelium (EC50: 1.1 x 10(-8) vs. 1.6 x 10(-7) M, p<0.05); and (2) in response to salbutamol, CRX with endothelium had a lower maximum relaxation response than CRX without endothelium (56.6 vs. 75.9%, p<0.05). At end-stage heart failure, (1) endothelium-intact CRX and LAD showed a significant decrease in sensitivity to isoproterenol compared to control (CRX-EC50: end-stage heart failure: 1.1 x 10(-7) vs. control: 1.8 x 10(-8)M,p<0.05; and LAD-EC50: end-stage heart failure: 8.8 x 10(-7) M vs. control: 8.3 x 10(-8) M, p<0.05); (2) LAD with endothelium showed greater maximum relaxation to salbutamol than LAD without endothelium (100.8 vs. 76.5%, p<0.05); and (3) CRX were significantly more sensitive to isoproterenol than LAD. These data suggest that coronary vascular tone via beta-adrenoceptor stimulation is coronary artery-dependent, and modulated not only by the heart failure state, but also by the presence of a functional endothelium.
充血性心力衰竭与心肌β-肾上腺素能受体功能异常有关。然而，心力衰竭时血管β-肾上腺素能受体改变的程度尚不清楚。因此，我们研究了快速心室起搏诱导的早期和终末期心力衰竭犬的左旋支（CRX）和左前降支（LAD）冠状动脉（有内皮和无内皮）中β-肾上腺素能受体介导的舒张作用（分别在250次/分钟起搏1周和4周）。在早期心力衰竭时，（1）有内皮的CRX对异丙肾上腺素比无内皮的CRX更敏感（半数有效浓度：1.1×10⁻⁸对1.6×10⁻⁷M，p<0.05）；（2）对沙丁胺醇的反应中，有内皮的CRX的最大舒张反应低于无内皮的CRX（56.6%对75.9%，p<0.05）。在终末期心力衰竭时，（1）与对照组相比，内皮完整的CRX和LAD对异丙肾上腺素的敏感性显著降低（CRX-半数有效浓度：终末期心力衰竭：1.1×10⁻⁷对对照组：1.8×10⁻⁸M，p<0.05；LAD-半数有效浓度：终末期心力衰竭：8.8×10⁻⁷M对对照组：8.3×10⁻⁸M，p<0.05）；（2）有内皮的LAD对沙丁胺醇的最大舒张作用大于无内皮的LAD（100.8%对76.5%，p<0.05）；（3）CRX对异丙肾上腺素的敏感性显著高于LAD。这些数据表明，通过β-肾上腺素能受体刺激的冠状动脉张力是冠状动脉依赖性的，不仅受心力衰竭状态的调节，还受功能性内皮存在的调节。
