Endogenous adenosine inhibits catecholamine contractile responses in normoxic hearts.
The importance of endogenous myocardial adenosine in attenuating catecholamine-elicited contractile responses was investigated in perfused oxygenated rat hearts. Perfusion of the isolated hearts with adenosine deaminase potentiated the isoproterenol-induced increases of three contractile variables (left ventricular pressure development and rates of both left ventricular pressure development and relaxation). The peak (maximal, within 30 s) and maintained (after 1 min) increases of the contractile variables caused by 10(-8) M isoproterenol were enhanced by 15-22 and 31-43%, respectively. Adenosine deaminase appeared in epicardial surface transudates of similarly perfused hearts, indicating that the enzyme had entered the myocardial interstitial space. Isoproterenol alone elevated the release of adenosine into coronary effluents of isoproterenol-stimulated hearts, and adenosine deaminase prevented the release of the nucleoside. The higher the level of adenosine in the effluent, the greater the reduction of the peak contractile variables. Phenylisopropyladenosine at 10(-8) M prevented the adenosine deaminase potentiation of 10(-9) M isoproterenol-induced contractile responses. The adenosine analogue at 10(-6) M blocked completely the isoproterenol-produced increases in the contractile variables. These results suggest that endogenous adenosine prevents full mechanical responsiveness to beta-adrenoceptor stimulation in the oxygenated myocardium. In addition, the findings support the notion that adenosine serves as an important negative feedback modulator in the oxygenated heart.
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000037:antagonists & inhibitors* / Q000502:physiology; D004357:Drug Synergism; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D010660:Phenylisopropyladenosine; D007288:Inosine; D000243:Adenosine Deaminase; D000241:Adenosine; D007545:Isoproterenol