Abstract

This is a resubmitted grant application to study endothelium- dependent relaxation in the coronary circulation of patients with coronary atherosclerosis. The application emphasizes the relationship of abnormalities in redox state and the generation and release of EDRF in these patients. Endothelium-dependent vasomotion will be studied in response to infusions of acetylcholine and substance P and increased blood flow during cardiac pacing. Vasomotor responses will assessed using intracoronary Doppler and quantitative angiography. These responses will be related to markers of antioxidant protection and oxidative stress in the coronary vasculature (coronary sinus concentrations of F2-isoprostanes and endothelin) and the systemic circulation (plasma antioxidant content and LDL susceptibility to oxidation). To examine the contribution of superoxide production to abnormal coronary activity, vasomotor responses will be examined following treatment with specific inhibitors of superoxide action.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL053398-05
Application #
6030688
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1995-07-01
Project End
2000-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118

  Publications

Gokce, N; Duffy, S J; Hunter, L M et al. (2001) Acute hypertriglyceridemia is associated with peripheral vasodilation and increased basal flow in healthy young adults. Am J Cardiol 88:153-9
Parker 3rd, C; Vita, J A; Freedman, J E (2001) Soluble adhesion molecules and unstable coronary artery disease. Atherosclerosis 156:417-24
Huang, A; Xiao, H; Samii, J M et al. (2001) Contrasting effects of thiol-modulating agents on endothelial NO bioactivity. Am J Physiol Cell Physiol 281:C719-25
Duffy, S J; Biegelsen, E S; Holbrook, M et al. (2001) Iron chelation improves endothelial function in patients with coronary artery disease. Circulation 103:2799-804
Duffy, S J; Gokce, N; Holbrook, M et al. (2001) Effect of ascorbic acid treatment on conduit vessel endothelial dysfunction in patients with hypertension. Am J Physiol Heart Circ Physiol 280:H528-34
Chen, K; Vita, J A; Berk, B C et al. (2001) c-Jun N-terminal kinase activation by hydrogen peroxide in endothelial cells involves SRC-dependent epidermal growth factor receptor transactivation. J Biol Chem 276:16045-50
Huang, A; Vita, J A; Venema, R C et al. (2000) Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem 275:17399-406
Xu, A; Vita, J A; Keaney Jr, J F (2000) Ascorbic acid and glutathione modulate the biological activity of S-nitrosoglutathione. Hypertension 36:291-5
Tomasian, D; Keaney, J F; Vita, J A (2000) Antioxidants and the bioactivity of endothelium-derived nitric oxide. Cardiovasc Res 47:426-35
Sherman, D L; Keaney Jr, J F; Biegelsen, E S et al. (2000) Pharmacological concentrations of ascorbic acid are required for the beneficial effect on endothelial vasomotor function in hypertension. Hypertension 35:936-41

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