Adenosine A(2a)-receptor activation increases contractility in isolated perfused hearts
Department of Physiology
Adenosine; Adenosine-5'-(N-ethylcarboxamide); Adrenergic beta-Antagonists; Animals; Atenolol; Drug Synergism; Heart; Male; Myocardial Contraction; Perfusion; Pertussis Toxin; Pressure; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2A; Receptors, Purinergic P1; Vasodilation; Vasodilator Agents; Virulence Factors, Bordetella; Xanthines
Life Sciences | Medicine and Health Sciences
Adenosine A(2a)-receptor activation enhances shortening of isolated cardiomyocytes. In the present study the effect of A(2a)-receptor activation on the contractile performance of isolated rat hearts was investigated by recording left ventricular pressure (LVP) and the maximal rate of LVP development (+dP/dt(max)). With constant-pressure perfusion, adenosine caused concentration-dependent increases in LVP and +dP/dt(max), with detectable increases of 4.1 and 4.8% at 10(-6) M and maximal increases of 12.0 and 11.1% at 10(-4) M, respectively. The contractile responses were prevented by the A(2a)-receptor antagonists chlorostyryl-caffeine and aminofuryltriazolotriazinyl-aminoethylphenol (ZM-241385) but were not affected by the beta(1)-adrenergic antagonist atenolol. The adenosine A(1)-receptor antagonist dipropylcyclopentylxanthine and pertussis toxin potentiated the positive inotropic effects of adenosine. The A(2a)-receptor agonists ethylcarboxamidoadenosine and dimethoxyphenyl-methylphenylethyl-adenosine also enhanced contractility. With constant-flow perfusion, 10(-5) M adenosine increased LVP and +dP/dt(max) by 5.5 and 6.0%, respectively. In the presence of the coronary vasodilator hydralazine, adenosine increased LVP and +dP/dt(max) by 7.5 and 7.4%, respectively. Dipropylcyclopentylxanthine potentiated the adenosine contractile responses with constant-flow perfusion in the absence and presence of hydralazine. These increases in contractile performance were also antagonized by chlorostyryl-caffeine and ZM-241385. The results indicate that adenosine increases contractile performance via activation of A(2a) receptors in the intact heart independent of beta(1)-adrenergic receptor activation or changes in coronary flow.
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Citation: Am J Physiol Heart Circ Physiol. 2000 Oct;279(4):H1472-81.
American journal of physiology. Heart and circulatory physiology
Monahan, Thomas S.; Sawmiller, Darrell R.; Fenton, Richard A.; and Dobson, James G. Jr., "Adenosine A(2a)-receptor activation increases contractility in isolated perfused hearts" (2000). Open Access Articles. 128.