Adenosine is not essential for exercise hyperaemia in the hindlimb in conscious dogs.

Abstract

SUMMARY1. The contribution of endogenous adenosine to the increase in hindlimb blood flow that occurs during treadmill exercise was evaluated in conscious dogs. We postulated that if adenosine is essential for the hindlimb hyperaemic response, then pharmacological treatment of the animals with adenosine receptor antagonists should decrease hindlimb blood flow during treadmill exercise.2. A total of twenty-three dogs were chronically instrumented for measurement of aortic blood pressure and hindlimb blood flow using electromagnetic or Doppler flow probes on the left external iliac artery. Measurements of arterial blood pressure, hindlimb blood flow and heart rate were made during steady-state treadmill exercise in both the presence and the absence of adenosine receptor antagonists. Four different protocols were performed using different routes of administration of two adenosine receptor antagonists. Aminophylline was used in most of the experiments, and the effects of the more potent antagonist, 8-phenyltheophylline, were also evaluated. In addition, the dogs exercised at varying intensities ranging from a low level of 5 5 km h-1 at 0 % gradient to a high intensity of 5-5 km h-' at 21 % gradient.3. Aminophylline given as a single intravenous dose, or as a constant infusion either intravenously or directly into the hindlimb artery, did not decrease hindlimb blood flow at low, moderate or high intensities of exercise. Likewise, the blockade of adenosine receptors with 8-phenyltheophylline, given systemically or as a bolus injection administered directly into the hindlimb circulation during moderate exercise, did not attenuate the hindlimb blood flow response.4. Our data demonstrate that exercise hyperaemia of the hindlimb is not reduced by antagonism of adenosine receptors. These findings are consistent with the hypothesis that adenosine is not an essential mediator of hindlimb vasodilatation during exercise.

Adenosine and nitric oxide in exercise‐induced human skeletal muscle vasodilatation

“…Moreover, adenosine receptor blockade with aminophylline (non‐selective) and 8‐phenyltheophylline during voluntary treadmill exercise supports (Metting et al. 1986) as well as rejects (Koch et al. 1990) a role of adenosine for exercise‐induced hyperaemia.…”

Bimodal distribution of vasodilator responsiveness to adenosine due to difference in nitric oxide contribution: implications for exercise hyperemia

“…In contrast, other studies failed to show any increase in venous Ado concentration (1, 39) or skeletal muscle Ado content (28). Furthermore, infusion of Ado receptor antagonists resulted in reduction of exercise hyperemia in some animal experiments (22, 27,29,38), whereas other studies found no reduction of exercise hyperemia (14,17).…”

“…In contrast, other studies failed to show any increase in venous Ado concentration (1, 39) or skeletal muscle Ado content (28). Furthermore, infusion of Ado receptor antagonists resulted in reduction of exercise hyperemia in some animal experiments (22, 27,29,38), whereas other studies found no reduction of exercise hyperemia (14,17).Although there are limited human studies regarding the role of Ado in exercise hyperemia, recent studies have suggested a likely contribution of Ado to exercise hyperemia by demonstrating 1) a direct linear relationship between interstitial concentration of Ado and femoral artery blood flow during dynamic one-legged knee extension exercise (13,20); 2) localization of vasodilating Ado A 1 , A 2A , and A 2B receptors on human vascular smooth muscle cells and vascular endothelial cells (21); and 3) that Ado infusion into the femoral artery caused increases in blood flow comparable to hyperemic levels during exercise (31). These latter authors also found that theophylline (Ado receptor antagonist) infusion during exercise decreased femoral arterial blood flow by 20%, suggesting an important role for Ado in human exercise hyperemia.…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…In addition, adenosine acts on presynaptic receptors to inhibit sympathetic nerve-mediated vasoconstriction (Fuglsang and Crone, 1987). However, in studies of canine gracilis muscle, it was concluded that, although released adenosine could contribute to exercise hyperemia, it is likely not to be the main factor, particularly in the initial stage (Ballard et al, 1987;Koch et al, 1990). Adenosine, acting via A 2A receptors, contributes up to 30% of the functional hyperemic response in the hindlimb of anesthetized cats (Poucher, 1996).…”