Increased vascular sensitivity to nitroglycerin in patients with hypercholesterolemia and peripheral endothelial dysfunction

The effects of the endothelium-dependent vasodilator acetylcholine, the endothelium-independent vasodilator nitroglycerin and a drug which inhibits basal nitric oxide (NO) release (L-NG-monomethyl-arginine [L-NMMA]) on the diameter of the radial artery and blood flow were studied in eight patients with hypercholesterolaemia (total cholesterol: 280 +/- 9 mg/dl, age 54 +/- 3 years) and eight healthy subjects of the same age (total cholesterol 197 +/- 12 mg/dl, age 51 +/- 4 years). Arterial diameter was measured by a recently developed high resolution ultrasound technique. Increasing concentrations of acetylcholine (10(-8) to 10(-6) mol/l) produced dose-dependent increases in flow rate in the healthy subjects (maximum +150% +/- 6% at 10(-6) mol/l), but much less in the patients with hypercholesterolaemia (+24% +/- 12%). L-NMMA caused comparable reductions in forearm blood flow in both groups. Nitroglycerin increased blood flow in the hypercholesterolaemia group to a significantly greater extent (+370% +/- 69%) than in the controls (+145 +/- 62%). The effects of acetylcholine, L-NMMA and nitroglycerin on radial artery diameter did not differ significantly between the two groups. The poor response (in terms of blood flow) to acetylcholine in the hypercholesterolaemia group points to an endothelial dysfunction in the arterial microcirculation. The fact that L-NMMA caused similar reductions in forearm blood flow in the controls and hypercholesterolaemia patients alike shows that basal NO synthase activity must be comparable in the two groups and therefore cannot be held responsible for the endothelial dysfunction. This endothelial dysfunction is linked with increased responsiveness to the endothelium-independent vasodilator nitroglycerin.