CIRCADIAN VARIATION IN CORONARY TONE IN PATIENTS WITH STABLE ANGINA -PROTECTIVE ROLE OF THE ENDOTHELIUM

Background Coronary endothelium plays a key role in the regulation of coronary tone, platelet adhesion, and aggregation, which are important factors in triggering acute cardiovascular events. However, its role in modulating the effects of circadian variations on coronary tone is not known. Methods and Results Responses of 72 nonstenotic coronary se gments to acetylcholine and nitroglycerin were measured in 12 patients with chronic stable angina at 6 AM and 1 PM. After baseline angiograp hy, three infusions of acetylcholine (10(-6), 10(-5), and 10(-4) mol/L ) were administered selectively into the left coronary artery, followe d by nitroglycerin. Diameters (in millimeters) of proximal, middle, an d distal segments were measured by quantitative techniques. Forty-seve n segments showed a constrictor response to acetylcholine (group 1, dy sfunctional endothelium), and 25 other segments showed a dilator respo nse (group 2, normally functioning endothelium). In group 1, the const rictor response to acetylcholine was significantly greater in the morn ing than in the afternoon (23+/-3% and 10+/-1%, mean+/-SEM, respective ly; P<.001), and the dilator response to nitroglycerin was also signif icantly greater in the morning than in the afternoon (19+/-2% and 11+/ -2%; P<.01). In group 2, the dilator response to acetylcholine did not differ significantly between the morning and afternoon (22+/-3% and 1 7+/-2%, respectively; P=NS), and the dilator response to nitroglycerin was also similar at both times of the day (30+/-3% and 28+/-4%, respe ctively; P=NS). Conclusions Coronary segments with dysfunctional endot helium exhibit an early morning exaggeration in vasomotor activity, wh ereas segments with normally functioning endothelium do not show circa dian variations. This suggests a potential protective role for the end othelium in modulating variations in coronary tone that may contribute to increased incidence of cardiovascular events in the early morning hours.