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(Circulation Research. 2003;93:691.)
© 2003 American Heart Association, Inc.

Editorials

Adenosine

A Modulator of the Cardiac Response to Stress

YingJie Chen, Robert J. Bache

From the Departments of Medicine and Physiology, University of Minnesota Health Sciences Center, Minneapolis, Minn.

Correspondence to Robert J. Bache, MD, University of Minnesota, Cardiovascular Division, Mayo Mail Code 508, 420 Delaware St SE, Minneapolis, MN 55455. E-mail bache001@umn.edu.

Key Words: myocardium • hypertrophy • G proteins • cardioprotection

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Adenosine has been recognized as a potentially important signaling molecule in the heart for nearly a half century. The original adenosine hypothesis proposed that production of adenosine by cardiac myocytes reflects the metabolic state of the myocardium and serves to regulate vasomotor tone in the coronary resistance vessels, thereby coupling blood flow to the energetic needs of the heart.¹ There are two major pathways for adenosine production in the cardiac myocyte. The transmethylation pathway involves the hydrolysis of S-adenosylhomocysteine (SAH) by SAH hydrolase to l-homocysteine and adenosine. A second pathway, the hydrolysis of AMP by 5'-nucleotidase, predominates during ischemic or hypoxic conditions.² According to the adenosine hypothesis, when the energy requirements of the heart increase, the increased rate of ATP hydrolysis would cause cytosolic free ADP levels to rise. In this situation, the myokinase reaction can utilize two molecules of ADP to produce one molecule each of ATP and AMP, the later being the substrate for 5'-nucleotidase to produce adenosine, which can enter the interstitial space to cause coronary vasodilation. Although this hypothesis for preserving the oxygen supply/demand relationship is attractive, it does not appear to operate during physiological conditions in the normal heart, since adenosine receptor inhibition does not decrease coronary blood flow or impair the increase of coronary flow during exercise.³

Implicit in the adenosine hypothesis is the assumption that during increased cardiac work, increases of cytosolic free [ADP] would be required to drive mitochondrial respiration and would serve to increase adenosine production. In fact, over a . . . [Full Text of this Article]

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				X. Xu, J. Fassett, X. Hu, G. Zhu, Z. Lu, Y. Li, J. Schnermann, R. J. Bache, and Y. Chen Ecto-5'-Nucleotidase Deficiency Exacerbates Pressure-Overload-Induced Left Ventricular Hypertrophy and Dysfunction Hypertension, June 1, 2008; 51(6): 1557 - 1564. [Abstract] [Full Text] [PDF]