title: The adenosine hypothesis of metabolic regulation of coronary flow in the light of newly recognized properties of the coronary endothelium.
abstract: With the aid of specially developed methods it has become possible to differentiate the purine metabolism of the heart at the level of the different myocardial tissues. This permits an evaluation of the biochemical mechanisms postulated by the adenosine hypothesis of the metabolic regulation of coronary blood flow. It is now clear that the coronary endothelium determines the metabolism of purines in both the interstitial and intravascular spaces of the myocardium on the basis of its great biochemical potency. Coronary flow increases evoked by adenosine and adenine nucleotides are mediated by the endothelium, which is apparently closely coupled to the vascular smooth muscle. These observations can still be reconciled with the adenosine hypothesis, albeit with considerable modification and extension. The results of our studies on purine metabolism in highly purified cardiomyocyte preparations from guinea-pig hearts, however, are completely at odds with the hypothesis. The intact cardiomyocyte is obviously unable to release adenosine, and is almost incapable of resynthesizing lost purine bodies. The impression is gained that the large amounts of adenosine and its degradatives detected, e.g., in the effluent of isolated hearts, are more likely to indicate myocardial damage than the production of a physiological mediator of coronary flow regulation. Presumably many experimental and clinical studies will need to be re-evaluated in the light of these interesting new aspects.
authors.affiliation: Physiologisches Institut, Universität München, FRG.
authors.forename: S
authors.initials: S
authors.lastname: Nees
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D011687:Purines / Q000378:metabolism
chemical_list: D011687:Purines; D000241:Adenosine