Several studies were designed to investigate strategies to improve endothelial dysfunction in patients with atherosclerosis and its risk factors. 1) Angiotensin converting enzyme (ACE) inhibition with enalaprilat acutely improved endothelium-dependent vasodilation in the coronary and peripheral vasculature of patients with atherosclerosis and its risk factors. This improvement was due to increased nitric oxide bioavailability with ACE inhibitors. Current studies are examining a) the role of angiotensin II receptor blockade in the improvement observed with ACE inhibitors, b) whether ACE inhibitors improve myocardial ischemia, c) whether the improvement relates to ACE genotype. 2) Glutathione improved endothelium-dependent peripheral vascular dilation in patients with atherosclerosis, a mechanism that was secondary to increased nitric oxide bioavailability. 3) Dobutamine, a beta receptor agonist used as an inotrope to increase myocardial work, dilates the coronary vasculature, whereas exercise constricts coronary arteries, indicating that use of pharmacologic stress can obscure coronary vasoconstriction that contributes to myocardial ischemia in patients with coronary atherosclerosis. 4) Arterial conduits used for bypass surgery (internal mammary arteries) have higher nitric oxide activity compared to saphenous vein grafts and atherosclerotic coronary arteries, which may account for the reduced incidence of atherosclerosis and thrombosis in arterial compared to venous conduits.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL005007-01
Application #
6162758
Study Section
Cell Biology Integrated Review Group (CB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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