Adenosine in the Local Regulation of Blood Flow: Some Controversies

Summary

Three major challenges to the adenosine hypothesis for the local regulation of blood flow are:

• a) the failure of adenosine deaminase to affect autoregulation of blood flow or block the effects of hypoxia or reactive hyperemia;

• b) the ineffectiveness of adenosine antagonists to completely block metabolically-induced vasodilation; and

• c) the lack of methodology for determination of interstitial fluid adenosine concentrations

First, evidence is lacking that an adequate concentration of adenosine deaminase can be achieved in the periarteriolar interstitial space, with intra-arterial infusion of the enzyme, to deaminate all of the adenosine that has access to the vascular smooth muscle of the resistance vessels. Hence, adenosine deaminase cannot be used as a reliable test of the adenosine hypothesis. Second, the adenosine antagonist, theophylline, has been shown to be as effective against endogenous adenosine as it is against exogenous adenosine if sufficient time elapses between administration of theophylline and the test of its effectiveness. Third, methods have been developed for measurements of cardiac and cerebral interstitial fluid adenosine concentrations and the results are compatible with a role for adenosine in blood flow regulation.