Lerman A, Holmes D R, Bell M R, Garratt K N, Nishimura R A, Burnett J C
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
Circulation. 1995 Nov 1;92(9):2426-31. doi: 10.1161/01.cir.92.9.2426.
The endothelium modulates vascular tone through release of vasodilating substances, such as endothelium-derived relaxing factors, and vasoconstricting substances, such as endothelin. Endothelin concentrations are elevated in humans with atherosclerosis and in hypercholesterolemic pigs. Furthermore, the endothelium-dependent vasodilator acetylcholine increases endothelin in hypercholesterolemia in association with coronary vasoconstriction. The present study was designed to test the hypotheses that coronary endothelial dysfunction in humans is characterized by enhanced coronary and circulating endothelin and that the vasoconstriction associated with acetylcholine results in further release of coronary endothelin.
Coronary and circulating endothelin concentrations were measured at baseline and during intracoronary acetylcholine administration in 20 patients undergoing diagnostic coronary angiography. Patients were divided into two groups on the basis of their response to intracoronary acetylcholine. Group 1 (n = 7) demonstrated a normal vasodilatory response, but group 2 (n = 13) demonstrated coronary vasoconstriction. Baseline coronary and circulating endothelin concentrations (as determined by coronary sinus and femoral artery measurements, respectively) were higher in patients who responded to acetylcholine with coronary vasoconstriction (group 2) than in group 1 patients (coronary sinus, 15.9 +/- 1.0 pg/mL versus 7.1 +/- 1.0 pg/mL; femoral, 14.1 +/- 0.9 pg/mL versus 6.8 +/- 1.0 pg/mL, respectively; P < .01). In response to intracoronary acetylcholine, a further increase in coronary endothelin was observed only in group 2; this increase correlated with changes in coronary artery diameter.
This study demonstrates that endothelin immunoreactivity is enhanced in the coronary and systemic circulation in humans with coronary endothelial dysfunction. Moreover, acetylcholine further increased coronary endothelin concentration in patients with coronary endothelial dysfunction and was associated with coronary vasoconstriction. These observations strongly support a role for endothelin as an early participant in and marker for coronary endothelial dysfunction in humans.
内皮细胞通过释放血管舒张物质（如内皮源性舒张因子）和血管收缩物质（如内皮素）来调节血管张力。在患有动脉粥样硬化的人类和高胆固醇血症猪中，内皮素浓度会升高。此外，内皮依赖性血管舒张剂乙酰胆碱在高胆固醇血症中与冠状动脉收缩相关，会增加内皮素的水平。本研究旨在验证以下假设：人类冠状动脉内皮功能障碍的特征是冠状动脉和循环内皮素增加，且与乙酰胆碱相关的血管收缩会导致冠状动脉内皮素进一步释放。
在20例接受诊断性冠状动脉造影的患者中，于基线期及冠状动脉内注射乙酰胆碱期间测量冠状动脉和循环内皮素浓度。根据患者对冠状动脉内乙酰胆碱的反应将其分为两组。第1组（n = 7）表现出正常的血管舒张反应，但第2组（n = 13）表现出冠状动脉收缩。对乙酰胆碱有冠状动脉收缩反应的患者（第2组）的基线冠状动脉和循环内皮素浓度（分别通过冠状窦和股动脉测量确定）高于第1组患者（冠状窦，分别为15.9±1.0 pg/mL对7.1±1.0 pg/mL；股动脉，分别为14.1±0.9 pg/mL对6.8±1.0 pg/mL；P <.01）。在冠状动脉内注射乙酰胆碱后，仅在第2组观察到冠状动脉内皮素进一步增加；这种增加与冠状动脉直径的变化相关。
本研究表明，在患有冠状动脉内皮功能障碍的人类中，冠状动脉和体循环中的内皮素免疫反应性增强。此外，乙酰胆碱使冠状动脉内皮功能障碍患者的冠状动脉内皮素浓度进一步升高，并与冠状动脉收缩相关。这些观察结果有力地支持了内皮素作为人类冠状动脉内皮功能障碍早期参与者和标志物的作用。
