Nitric oxide production by coronary conductance and resistance vessels in hypercholesterolemia patients

NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide (NO) synthesis, was used to investigate the effects of inhibition of NO synthesis on the coronary conductance and resistance vessels in hypercholesterolemic patients. Acetylcholine (3 and 30 micrograms/min) was administered to 10 hypercholesterolemic and 10 control patients before and after L-NMMA (25 micromol/min) infusion. Epicardial coronary diameter was measured by quantitative angiography, and coronary blood flow (CBF) was derived from Doppler flow-velocity and coronary diameter measurements. In hypercholesterolemic patients, acetylcholine-induced dilation of epicardial arteries was attenuated, and the percentage increase in CBF caused by acetylcholine was smaller than that in control patients. L-NMMA attenuated acetylcholine-induced dilation of epicardial arteries in control patients. L-NMMA had no effect on CBF responses to acetylcholine in both patient groups. L-NMMA significantly decreased the baseline coronary diameter and CBF in both groups. These results indicated that hypercholesterolemia impaired the acetylcholine-induced dilation of the conductance and resistance coronary vessels. This impairment in the conductance vessels was dependent on NO production; that of resistance vessels was not. The basal release of NO in conductance and resistance vessels was preserved in hypercholesterolemic patients.