Recent studies have shown that a brief exposure to ischemia renders the heart better able to tolerate a subsequent longer ischemic insult, a phenomenon called ischemic preconditioning. The first hypothesis of this proposal is that ischemic preconditioning is accompanied by enhanced and sustained gene expression of HSPs in the heart of rats and rabbits. In addition to HSP70, the applicants will explore the role of other stress proteins such as HSP27, 60, and 90. The second hypothesis is that quercitine, an inhibitor of the heat shock transcription factor, blocks preconditioning by blocking the synthesis of HSPs. The third hypothesis is that oxygen radicals directly trigger the preconditioning and that scavenging of radicals by antioxidants attenuates the protection derived from preconditioning and reduces the expression of HSPs. The fourth hypothesis is that activation of adenosine A1-receptors during preconditioning results in enhanced expression of HSPs. The applicants will examine the effects of adenosine agonists and antagonists on preconditioning and HSP synthesis in rats as well as rabbits. The fifth hypothesis is that synthesis of HSPs mediates the second window of protection which develops 24 hours after ischemic preconditioning. The applicants anticipate answering the following questions: (1) whether preconditioning induces the expression of HSP27, 60, and 90 in addition to HSP70; (2) whether HSPs are involved in preconditioning early or late; (3) whether oxygen radicals trigger the preconditioning by inducing HSP; and (4) whether adenosine receptor activation induces expression of HSPs resulting in preconditioning.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL051045-04
Application #
2735223
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1995-08-01
Project End
1999-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
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