The Effects of Diabetes Mellitus on the Relationship Between Myocardial Adenosine Production and Coronary Vascular Resistance
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
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Adenosine, a product of adenosine triphosphate metabolism, has been proposed as a mediator of coronary vascular resistance CVR in the normal heart. This study was designed to determine if the relationship between adenosine production and CVR is altered in diabetes mellitus, a metabolic disorder characterized by a decrease in insulin function and associated with serious cardiac complications. The relationship between myocardial adenosine production and CVR was studied in normal and chemically-induced diabetic rats and dogs. There was a significant negative correlation between myocardial adenosine content and CVR in the normal rats, but not in the diabetic rats. Diabetic rats exhibited decreased coronary blood flow CBF and impaired ventricular pressure development and contractility as compared to controls. Myocardial adenosine content was elevated in the diabetic rats without an associated change in CVR. The effects of exercise conditioning on the relationship between myocardial adenosine content and CVR were also tested because exercise training has been shown by others to increase insulin binding and glucose uptake in blood cells and skeletal muscle, respectively, in both normal and diabetic individuals. Following an eight - week running program, the correlation between myocardial adenosine content and CVR was restored to normal in the diabetic rats. Studies were conducted in dogs for the purpose of studying adenosine release, or the product of CBF and coronary sinus-arterial adenosine concentrations. Under basal conditions, diabetic dogs exhibited decreased CVR and increased coronary blood flow, cardiac work and myocardial oxygen consumption as compared to normal animals. Interestingly, basal adenosine release was not different between the two groups and a significant negative correlation between adenosine release and coronary vasodilatation during intravenous norepinephrine infusion was evident in normal dogs only.
- Anatomy and Physiology
- Medicine and Medical Research
- Organic Chemistry