Adenosine, the heart, and coronary circulation.

Abstract

Adenosine is known to regulate myocardial and coronary circulatory functions. Adenosine not only dilates coronary vessels, but attenuates 0-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., A, and A 2 receptors). A, adenosine receptors, located in atrial and ventricular myocardium and sinoatrial/atrioventricular nodes, are responsible for inhibition of adenylyl cyclase activity. A 2 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. (Hypertension 1991;18:565-574)

Impact of Adenosine Receptor Signaling and Metabolism on Pathophysiology in Patients with Chronic Heart Failure

“…Interestingly, catecholamine, angiotensin, aldosterone, and cytokines are known to be involved in the pathophysiology of CHF (2)(3)(4)(5), as evidenced by the fact that β-adrenoceptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, and aldosterone receptor antagonists are widely accepted as drugs for CHF (6,7). Adenosine has biological effects on various tissues (8)(9)(10). Since several lines of evidence (9,10) support the idea that adenosine is cardioprotective against deleterious sequels in CHF as well as ischemic heart disease, it is intriguing and important to analyze the adenosine receptor-or adenosine metabolismrelated genes using DNA microarray analysis.…”

“…Adenosine has biological effects on various tissues (8)(9)(10). Since several lines of evidence (9,10) support the idea that adenosine is cardioprotective against deleterious sequels in CHF as well as ischemic heart disease, it is intriguing and important to analyze the adenosine receptor-or adenosine metabolismrelated genes using DNA microarray analysis. Adenosine is known to be an endogenous nucleoside acting as a cardioprotective substance that modulates numerous physiological processes, including the regulation of coronary blood flow (9,10).…”

Adenosine and amrinone reverse felypressin-induced depression of myocardial tissue oxygen tension in dogs

“…The major actions of ADO are 1) vasodilation and afterload reduction through a decrease of peripheral resistance, 2) increase of both cardiac output and stroke volume without inducing tachycardia and 3) increase of CBF and decrease of cardiac oxygen consumption. 13 These hemodynamic effects appear to be mediated by ADO receptors, 14,15 with the major ADO receptors designated as A1 and A2. A1 receptors mainly mediate inhibition of norepinephrine release, 16 inhibition of excessive myocardial contraction induced by beta-stimulation 17,18 and delay of stimulation conduction velocity, 14 all actions which reduce myocardial oxygen demand.…”

Antiarrhythmic Efficacy of Dipyridamole in Treatment of Reperfusion Arrhythmias

“…22 Therefore, it is possible that the antiarrhythmic efficacy of dipyridamole is due to improved coronary flow. However, in the present study, intracoronary nitroglycerin showed little effect toward prevention of reperfusion arrhythmias.…”