Blood flow in heart and skeletal muscle is normally modulated, by unknown local mechanisms, to follow changes in the metabolic needs of these tissues. The long-term goal of this work is to identify these mechanisms. Ultimately such knowledge would aid in the development of better therapeutic measures for correcting blood flow abnormalities in heart and skeletal muscle. It is currently hypothesized that muscle blood flow is regulated by an influence of interstitial adenosine concentration on the diameter of vessels within the tissue.
The specific aims for this project are: 1) to establish the kinetics of each of the processes which remove adenosine from the interstitial space of muscle tissue, and 2) to apply this information in several tests of the hypothesis that adenosine mediates exercise hyperemia. A rat cremaster muscle preparation will be used to study arteriolar diameter response to topically-applied adenosine and to muscle exercise with a video-microscope system. In addition, HPLC techniques will be used to measure the adenosine concentration in solutions equilibrated with the surface of the muscle tissue. The microvascular observations, adenosine assay results, and a model of interstitial adenosine diffusion will be used together to make estimates of interstitial adenosine concentration and gradients in interstitial adenosine concentrations which exist in a variety of experimental situations. Specific experiments planned to determine: 1) the interstitial diffusion coefficient for adenosine, 2) the rate constants for adenosine removal from the interstitium by cellular uptake, interstitial degradation, and flow washout, and 3) the interstitial adenosine concentration which exists during different rates of muscle exercise.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032686-03
Application #
3344091
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1984-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Mohrman, D E; Heller, L J (1990) Transcapillary adenosine transport in isolated guinea pig and rat hearts. Am J Physiol 259:H772-83
Mohrman, D E (1988) Adenosine handling in interstitia of cremaster muscle studied by bioassay. Am J Physiol 254:H369-76