Hypertension, Vol 18, 565-574, Copyright © 1991 by American Heart Association
M Hori and M Kitakaze
Adenosine is known to regulate myocardial and coronary circulatory
functions. Adenosine not only dilates coronary vessels, but attenuates
beta-adrenergic receptor-mediated increases in myocardial contractility and
depresses both sinoatrial and atrioventricular node activities. The effects
of adenosine are mediated by two distinct receptors (i.e., A1 and A2
receptors). A1 adenosine receptors, located in atrial and ventricular
myocardium and sinoatrial/atrioventricular nodes, are responsible for
inhibition of adenylyl cyclase activity. A2 adenosine receptors, located in
coronary endothelial and smooth muscle cells, are responsible for
stimulation of this enzyme activity. During increased myocardial oxygen
demand due to rapid pacing and exercise, although both coronary blood flow
and adenosine concentrations in the myocardium and coronary efflux
increased, there is no clear consensus explaining its cause and effect
relation at present. However, ischemia/reperfusion- induced coronary
hyperemia is believed to be mostly attributed to released adenosine, and it
has been proven that adenosine attenuates the severity of ischemia due to
its coronary vasodilatory action. The beneficial effects of adenosine
during ischemia/reperfusion processes do not seem simple. This is because
myocardial ischemia and reperfusion injury is caused by 1) activated
leukocytes and platelets, 2) ATP depletion and calcium overload of
myocardium, and 3) catecholamine release from the presynaptic nerves as
well as 4) the impaired coronary circulation. Intriguingly adenosine
attenuates all of these deleterious actions and thereby attenuates
ischemia/reperfusion injury. Indeed, adenosine attenuates the severity of
contractile dysfunction (myocardial stunning) and limits the infarct size.
Thus, administration of adenosine or potentiators of adenosine production
in the ischemic myocardium may be beneficial for the attenuation of
ischemic and reperfusion injuries, although further clinical investigations
are necessary.
ARTICLES
Adenosine, the heart, and coronary circulation
First Department of Medicine, Osaka University School of Medicine, Japan.
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