OBJECTIVES: This study was designed to determine whether enhanced sensitivity to exogenous nitrovasodilators is present in the coronary arteries of patients with impaired endothelium-dependent dilation. BACKGROUND: Animal studies have demonstrated that the dilator response to exogenous nitrovasodilators is exaggerated in the setting of endothelial dysfunction (diminished nitric oxide activity). Whether such relative hyperresponsiveness to exogenous nitrates occurs and is important in humans is unknown. METHODS: We assessed coronary vasomotion in 110 patients (mean [+/- SD] age 56 +/- 10 years) by serial intracoronary infusions of acetylcholine (10(-8) to 10(-6) mol/liter) to test endogenous nitric oxide and nitroglycerin (40 micrograms) to test responses to exogenous nitrovasodilators. RESULTS: The vasomotor response to 10(-6) mol/liter of acetylcholine differed between patients with (n = 95) and those without (n = 15) normal endothelial dysfunction (-21 +/- 14% vs. 12 +/- 8%, respectively, p < 0.001). However, neither the dilator response to nitroglycerin (21 +/- 14% vs. 18 +/- 13%) nor the baseline diameter differed between those with endothelial dysfunction and normal function, respectively. There was no correlation between the magnitude of the dilator response to nitroglycerin and acetylcholine. The response to nitroglycerin was decreased with increasing age (r = -0.21, p = 0.03) but was not related to any other demographic factors or to the angiographic appearance of the vessel. CONCLUSIONS: The coronary vasodilator response to nitroglycerin is not significantly enhanced in patients with impaired endothelium-dependent dilation but decreases with increasing age. This finding provides indirect evidence that basal coronary tone is not increased in patients with endothelial dysfunction and that supersensitivity to exogenous nitrates is not clinically important in humans.
OBJECTIVES: This study was designed to determine whether enhanced sensitivity to exogenous nitrovasodilators is present in the coronary arteries of patients with impaired endothelium-dependent dilation. BACKGROUND: Animal studies have demonstrated that the dilator response to exogenous nitrovasodilators is exaggerated in the setting of endothelial dysfunction (diminished nitric oxide activity). Whether such relative hyperresponsiveness to exogenous nitrates occurs and is important in humans is unknown. METHODS: We assessed coronary vasomotion in 110 patients (mean [+/- SD] age 56 +/- 10 years) by serial intracoronary infusions of acetylcholine (10(-8) to 10(-6) mol/liter) to test endogenous nitric oxide and nitroglycerin (40 micrograms) to test responses to exogenous nitrovasodilators. RESULTS: The vasomotor response to 10(-6) mol/liter of acetylcholine differed between patients with (n = 95) and those without (n = 15) normal endothelial dysfunction (-21 +/- 14% vs. 12 +/- 8%, respectively, p < 0.001). However, neither the dilator response to nitroglycerin (21 +/- 14% vs. 18 +/- 13%) nor the baseline diameter differed between those with endothelial dysfunction and normal function, respectively. There was no correlation between the magnitude of the dilator response to nitroglycerin and acetylcholine. The response to nitroglycerin was decreased with increasing age (r = -0.21, p = 0.03) but was not related to any other demographic factors or to the angiographic appearance of the vessel. CONCLUSIONS: The coronary vasodilator response to nitroglycerin is not significantly enhanced in patients with impaired endothelium-dependent dilation but decreases with increasing age. This finding provides indirect evidence that basal coronary tone is not increased in patients with endothelial dysfunction and that supersensitivity to exogenous nitrates is not clinically important in humans.