Cardiac electrophysiological actions of adenosine

Abstract

Adenosine, an endogenous nucleoside, modulates heart functions via cell membrane receptors. This review focuses on the A1 adenosine receptor‐mediated electrophysiological effects on cardiac myocytes. Activation of A1 adenosine receptors leads to reductions of heart rate, atrioventricular nodal conduction, and atrial contractile force, and to an attenuation of the effects of β‐adrenergic stimulation on myocardium. The ionic mechanisms and the receptor‐effector coupling systems that underly the inhibitory effects of adenosine are discussed. Drug Dev. Res. 45:420–426, 1998. © 1998 Wiley‐Liss, Inc.

Adenosine-Stimulated Atrial Natriuretic Peptide Release Through A 1 Receptor Subtype

“…4 In the cardiovascular system, adenosine causes coronary vasodilation, the reduction of heart rate and cardiac contractility, and the attenuation of stimulatory actions of catecholamines on heart. 5 Endogenous release of adenosine during myocardial ischemia and hypoxia induces a potent protective effect in paracrine and autocrine ways. 6 Adenosine produced during a brief period of ischemia or exogenously administered adenosine causes a cardioprotective effect manifested by a reduction of infarct size or decreased myocardial stunning during ischemic preconditioning 7 via activation of A 1 and A 3 receptor subtypes.…”

“…Adenosine has been shown to play a protective role against ischemic injury, including coronary vasodilation, the reduction of heart rate, and cardiac contractility. 5 Together with our findings that adenosine exhibits a direct stimulatory effect on ANP release with negative inotropism, ANP released from atria by adenosine signaling may support beneficial effects on the overloaded heart by decreasing cardiac workload and dilating coronary artery. In conclusion, the A 1 receptor subtype is responsible for adenosine-induced ANP release and negative inotropism through AC-cAMP pathway.…”

“…6 Adenosine produced during a brief period of ischemia or exogenously administered adenosine causes a cardioprotective effect manifested by a reduction of infarct size or decreased myocardial stunning during ischemic preconditioning 7 via activation of A 1 and A 3 receptor subtypes. 5,8 Myocardial adenosine and ADP levels are increased during hypoxia and in severely hypertrophied hearts. Therefore, adenosine can exert effects on the ischemic or overloaded heart that are of considerable scientific and potential therapeutic interest.…”

AMP does not induce torpor

“…Adenosine binds specific G-protein linked cell surface receptors, of which there are multiple forms (12). When activated by adenosine, the A 1 receptor, which is highly expressed in the sino-atrial and atrial-ventricular nodes of the heart, activates adenosine-sensitive potassium channels, leading to hyperpolarization of the cell with the resultant slowing of nodal firing (25,35). The slowing of heart rate induced by adenosine (10,11,28) is also observed with administration of AMP (Fig.…”

Adenosine deaminase: Functional implications and different classes of inhibitors

“…181,182 Hence, it has been suggested to potentiate the level of such endogenous extracellular adenosine in an event-speci®c manner, that is, to reduce breakdown of adenosine by using adenosine deaminase and adenosine kinase inhibitors. 190,191 There are recent reports that adenosine deaminase inhibitors attenuate myocardial ischemic injury and improve postischemic recovery of contractile function and metabolism through endogenous myocardial adenosine enhancement and ATP preservation. Several groups have studied the effects of adenosine kinase and adenosine deaminase inhibitors on the release of adenosine in the central nervous system.…”