Melchert P J, Duncker D J, Traverse J H, Bache R J
Division of Cardiology, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Am J Physiol. 1999 Aug;277(2 Pt 2):H617-25. doi: 10.1152/ajpheart.1999.277.2.H617.
In the hypertrophied heart, increased extravascular forces acting to compress the intramural coronary vessels might require augmentation of metabolic vasodilator mechanisms to maintain adequate coronary blood flow. Vascular smooth muscle ATP-sensitive potassium (K(+)(ATP)) channel activity is important in metabolic coronary vasodilation, and adenosine contributes to resistance vessel dilation in the hypoperfused heart. Consequently, this study was performed to determine whether K(+)(ATP) channels and adenosine have increased importance in exercise-induced coronary vasodilation in the hypertrophied left ventricle. Studies were performed in dogs in which banding of the ascending aorta had resulted in a 66% increase in left ventricular mass in comparison with historic normal animals. Treadmill exercise resulted in increases of coronary blood flow that were linearly related to the increase of heart rate or rate-pressure product. During resting conditions, K(+)(ATP) channel blockade with glibenclamide caused a 17 +/- 5% decrease in coronary blood flow, similar to that previously observed in normal hearts. Unlike normal hearts, however, glibenclamide blunted the increase in coronary flow that occurred during exercise, causing a significant decrease in the slope of the relationship between coronary flow and the rate-pressure product. Adenosine receptor blockade with 8-phenyltheophylline did not alter coronary blood flow at rest or during exercise. Furthermore, even after K(+)(ATP) channel blockade with glibenclamide, the addition of 8-phenyltheophylline had no effect on coronary blood flow. This finding was different from normal hearts, in which the addition of adenosine receptor blockade after glibenclamide impaired exercise-induced coronary vasodilation. The data suggest that, in comparison with normal hearts, hypertrophied hearts have increased reliance on opening of K(+)(ATP) channels to augment coronary flow during exercise. Contrary to the initial hypothesis, however, adenosine was not mandatory for exercise-induced coronary vasodilation in the hypertrophied hearts either during control conditions or when K(+)(ATP) channel activity was blocked with glibenclamide.
在肥厚性心脏中，作用于压迫壁内冠状动脉血管的血管外作用力增加，可能需要增强代谢性血管舒张机制以维持足够的冠状动脉血流量。血管平滑肌ATP敏感性钾（K(+)(ATP)）通道活性在代谢性冠状动脉舒张中起重要作用，腺苷有助于低灌注心脏中阻力血管的舒张。因此，进行本研究以确定K(+)(ATP)通道和腺苷在肥厚性左心室运动诱导的冠状动脉舒张中是否具有更大的重要性。研究在犬身上进行，其中升主动脉结扎导致左心室质量相较于历史正常动物增加了66%。跑步机运动导致冠状动脉血流量增加，且与心率或心率-压力乘积的增加呈线性相关。在静息状态下，用格列本脲阻断K(+)(ATP)通道导致冠状动脉血流量下降17±5%，与先前在正常心脏中观察到的情况相似。然而，与正常心脏不同的是，格列本脲使运动期间发生的冠状动脉血流量增加减弱，导致冠状动脉血流量与心率-压力乘积之间关系的斜率显著降低。用8-苯基茶碱阻断腺苷受体在静息或运动时均未改变冠状动脉血流量。此外，即使在用格列本脲阻断K(+)(ATP)通道后，添加8-苯基茶碱对冠状动脉血流量也没有影响。这一发现与正常心脏不同，在正常心脏中，在格列本脲后添加腺苷受体阻断会损害运动诱导的冠状动脉舒张。数据表明，与正常心脏相比，肥厚性心脏在运动期间增加了对K(+)(ATP)通道开放以增加冠状动脉血流量的依赖。然而，与最初的假设相反，无论是在对照条件下还是在用格列本脲阻断K(+)(ATP)通道活性时，腺苷对于肥厚性心脏运动诱导的冠状动脉舒张都不是必需的。
