Role of adenosine in coronary vasodilation during exercise.

Abstract

This study examined the hypothesis that increases in myocardial blood flow during exercise are mediated by adenosine-induced coronary vasodilation. Active hyperemia associated with graded treadmill exercise and coronary reactive hyperemia were examined in chronically instrumented awake dogs during control conditions, after intracoronary infusion of adenosine deaminase (5 units/kg/min for 10 minutes), and after adenosine receptor blockade with 8-phenyltheophylline. Both adenosine deaminase and 8-phenyltheophylline caused a rightward shift of the dose-response curve to intracoronary adenosine; 8-phenyltheophylline was significantly more potent than adenosine deaminase. Adenosine deaminase caused a 33 +/- 7 to 39 +/- 3% decrease in reactive hyperemia blood flow following coronary occlusions of 5-20 seconds duration, respectively, while 8-phenyltheophylline produced a 40 +/- 6 to 62 +/- 8% decrease in reactive hyperemia. Increasing myocardial oxygen consumption during treadmill exercise was associated with progressive increase of coronary blood flow. Neither adenosine deaminase nor 8-phenyltheophylline attenuated the increase in coronary blood flow or the decrease of coronary vascular resistance during exercise. Neither agent altered the relation between myocardial oxygen consumption and coronary blood flow. Thus, although both adenosine deaminase and 8-phenyltheophylline antagonized coronary vasodilation in response to exogenous adenosine and blunted coronary reactive hyperemia, neither agent impaired coronary vasodilation associated with increased myocardial oxygen requirements produced by exercise. These findings fail to support a substantial role for adenosine in mediating coronary vasodilation during exercise.

Role of K+ ATP channels and adenosine in the regulation of coronary blood flow during exercise with normal and restricted coronary blood flow.

“…In dogs with chronically implanted pericardial catheters, graded exercise was associated with progressive increases of pericardial fluid adenosine concentrations (22)(23)(24), with a positive correlation between adenosine concentrations and coronary blood flow. However, Bache et al (1) reported that adenosine receptor blockade with 8-phenyltheophylline or increased adenosine catabolism with adenosine deaminase did not alter exercise-induced increases in coronary blood flow. Taken together, these findings indicate that, although myocardial adenosine production increases during exercise, it is not obligatory for maintenance of coronary blood flow at rest or during exercise in the normal heart.…”

“…Previous studies have demonstrated that endogenous adenosine is not obligatory for maintaining coronary blood flow during normal arterial inflow. Thus, studies in anesthetized open-chest dogs (15)(16)(17)(18)(19) and awake dogs (1,20) failed to demonstrate an effect of intracoronary adenosine deaminase (15)(16)(17), or adenosine receptor blockade with intravenous aminophylline (18, 19) or 8-phenyltheophylline (1, 20), on (21) examined the effect of exercise on myocardial adenosine production. They found that treadmill exercise in dogs resulted in a fivefold increase in myocardial adenosine content, with a doubling of the coronary arterio-venous adenosine content difference.…”

“…A solid state micromanometer (model P5; Konigsberg Instruments, Inc., Pasadena, CA) was also introduced into the left ventricle through the area of the apex. Approximately 1.5 cm of the proximal left anterior descending coronary artery (LAD) 1 was dissected free, and a Doppler flow probe (Craig Hartley Methodist Hospital, Houston, TX) was positioned around the artery. Immediately distal to the flow probe, a hydraulic occluder (3.0 mm o.d.)…”

“…This close coupling, which is especially apparent during exercise, has been suggested to depend on messengers released from the myocardium or vascular endothelium. However, specific blockers of established endogenous vasodilators such as adenosine (1), prostacyclin (2), and nitric oxide (3) have not been found to impair coronary blood flow during exercise, indicating that these vasodilators are not mandatory for regulation of coronary vasomotor tone during exercise with normal coronary arterial inflow. In contrast, these vasodilator mechanisms can contribute significantly to regulation of coronary vasomotor tone during exercise in the presence of myocardial hypoperfusion.…”

The optimal measure of microvascular function with velocity time integral for cardiovascular risk prediction

“…19 This triggers a number of mechanisms, some of which involve endothelium-derived nitric oxide, adenosine, K + ATP channels, and certain cyclooxygenase-derived metabolites to maintain the elevated flow velocity during the period of reactive hyperaemia. [20][21][22][23][24] Peak hyperaemic blood flow is only partially regulated by the release of endotheliumderived nitric oxide. 25 On the other hand, among the various vasodilators, such as prostaglandins and endotheliumderived hyperpolarizing factor, released from the endothelium, nitric oxide is the primary mediator of FMD.…”