Recent studies have demonstrated that the endothelium-dependent vascular relaxation of hypercholesterolemic animals and humans is impaired. We undertook the present investigation to determine the role of nitric oxide, one of the several factors produced by the endothelium, in this abnormal vasodilator response to endothelium-dependent agents. For this purpose, we studied the effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of the synthesis of nitric oxide by endothelial cells, on basal vascular tone and on the responses to acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (a smooth muscle dilator). Twenty hypercholesterolemic patients (plasma cholesterol > 240 mg/dl; age 49+8 years; 13 men and 7 women) and 18 normal controls (47+7 years; 11 men and 7 women). Drugs were given into the brachial artery and the response of the forearm vasculature was measured by strain guage plethysmography. The vasodilator response to acetylcholine was impaired in hypercholesterolemic patients compared to normal controls; however, no difference was found in the response to sodium nitroprusside. The reduction in basal blood flow produced by L-NMMA was similar in hypercholesterolemic and controls. As shown previously, L-NMMA significantly blunted the response to acetylcholine in normal controls; however, the response to acetylcholine was not modified by L-NMMA in hypertensive patients. These findings indicate that basal production of nitric oxide by endothelial cells is not significantly impaired in hypercholesterolemic patients. However, a deficit in the release of nitric oxide during stimulation with endothelium-dependent vasodilators may account for the abnormal endothelium mediated vasodilation of these patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL004919-01
Application #
3843419
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code