Background Endothelium-dependent modulation of coronary vasomotion dur
ing increased sympathetic tone remains unclear in normal and atheroscl
erotic human coronary arteries. Methods and Results we evaluated the r
ole of endothelium-derived nitric oxide in vasomotion during isometric
exercise in normal subjects (n = 7) and in patients with coronary art
ery disease (CAD) (n = 10). Coronary blood flow and epicardial coronar
y artery diameter to the handgrip test were measured before and after
intracoronary administration of 100 mu mol/min of N-G-monomethyl L-arg
inine (L-NMMA). Heart rate and aortic blood pressure increased during
handgrip test. Handgrip test caused a significant dilation in the diam
eter of the epicardial coronary artery in normal subjects (9.9% +/- 3.
9%, mean +/- SD) and in the diameter of smooth segments of patients wi
th CAD (5% +/- 3.7%, p < 0.05 vs normal subjects). In contrast, the di
ameter of irregular segments in patients with CAD decreased during han
dgrip test (-9.8 +/- 3.9%). After L-NMMA, the epicardial coronary arte
ry significantly increased during handgrip test compared with before L
-NMMA in normal subjects. L-NMMA did not have any effect on handgrip t
est induced vasodilation in the smooth segments and vasoconstriction i
n the irregular segments in the patients with CAD. Handgrip test-induc
ed increases in coronary blood flow did not change after L-NMMA in bot
h groups. Conclusions Nitric oxide does not play a major role in HNG-i
nduced vasodilation in epicardial and microcirculatory vessels in norm
al human coronary circulation. Although the decreased release in nitri
c oxide may modulate the abnormal response of the epicardial coronary
artery to handgrip test, this does not explain the paradoxic constrict
ive response from the depressed but still dilatory response in the pat
ients with CAD.