Takamura M, Parent R, Cernacek P, Lavallée M
Department of Medicine, Institut de Cardiologie de Montréal, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada H1T 1C8.
J Appl Physiol (1985). 2000 Nov;89(5):2041-8. doi: 10.1152/jappl.2000.89.5.2041.
We hypothesized that endothelin (ET) release during exercise may be triggered by alpha-adrenergic-receptor activation and thereby influence coronary hemodynamics and O(2) metabolism in dogs. Exercise resulted in coronary blood flow increases (to 1.88+/-0.26 from 1.10+/- 0.12 ml x min(-1) x g(-1)) and in a fall (P<0.01) in coronary sinus O(2) saturation (17.4+/-1.5 to 9.6+/-0.7 vol%), whereas myocardial O(2) consumption (MVO(2)) increased (109+/-13% from 145+/-16 microl O(2) min(-1) x g(-1)). Tezosentan, a dual ET(A)/ET(B)-receptor blocker, slightly reduced mean arterial pressure (MAP) and increased heart rate throughout exercise. The relationship between coronary sinus O(2) saturation and MVO(2) was shifted upward (P<0.05) after tezosentan administration; i.e., as MVO(2) increased during exercise, coronary sinus O(2) saturation was disproportionately higher after ET-receptor blockade. After propranolol, tezosentan resulted in significant decreases (P<0.05) in left ventricular pressure, the first derivative of left ventricular pressure over time, and MAP during exercise. As MVO(2) increased during exercise, coronary sinus O(2) saturation levels after tezosentan became superimposable over those observed before ET-receptor blockade. Thus dual blockade of ET(A)/ET(B) receptors alters coronary hemodynamics and O(2) metabolism during exercise, but ET activity failed to increase beyond baseline levels.
我们推测，运动过程中内皮素（ET）的释放可能由α-肾上腺素能受体激活触发，从而影响犬的冠状动脉血流动力学和氧代谢。运动导致冠状动脉血流量增加（从1.10±0.12 ml·min⁻¹·g⁻¹增至1.88±0.26），同时冠状窦氧饱和度下降（P<0.01）（从17.4±1.5降至9.6±0.7 vol%），而心肌氧消耗（MVO₂）增加（从145±16 μl O₂·min⁻¹·g⁻¹增至109±13%）。替唑生坦是一种ET(A)/ET(B)双重受体阻滞剂，在整个运动过程中使平均动脉压（MAP）略有降低并使心率增加。给予替唑生坦后，冠状窦氧饱和度与MVO₂之间的关系向上移动（P<0.05）；即，在运动过程中随着MVO₂增加，ET受体阻断后冠状窦氧饱和度异常升高。给予普萘洛尔后，替唑生坦导致运动过程中左心室压力、左心室压力随时间的一阶导数和MAP显著降低（P<0.05）。随着运动过程中MVO₂增加，替唑生坦后的冠状窦氧饱和度水平变得与ET受体阻断前观察到的水平重叠。因此，ET(A)/ET(B)受体的双重阻断在运动过程中改变了冠状动脉血流动力学和氧代谢，但ET活性未能增加到基线水平以上。
