Adenosine release by the isolated guinea pig heart in response to isoproterenol, acetylcholine, and acidosis: the minimal role of vascular endothelium.
The objective of this study was to determine the contribution of endothelial cells to adenosine appearing in venous effluent of isolated perfused guinea pig hearts. The adenine nucleotide pool of endothelial cells was selectively labelled by infusing 3H-adenosine (5 X 10(-8) M) into the heart for 30 minutes. Selective labelling of the endothelial adenine nucleotides was confirmed by measuring the relative specific activities of the nucleotides of coronary endothelial cells (removed from the heart by enzyme treatment). Endothelial ATP, ADP, and AMP had relative specific activities that were 49, 25, and 7 times higher, respectively, than their nucleotide counterparts in total myocardial tissue. Isoproterenol increased the release of both total adenosine and radioactive adenosine, but the relative specific activity of venous adenosine decreased dramatically. Acetylcholine, at a concentration that caused no change in left ventricular pressure but caused a decrease in coronary vascular resistance, increased the release of total adenosine. However, both radioactive adenosine release and the relative specific activity of venous effluent adenosine were decreased with acetylcholine. Infusion of hydrochloric acid caused a sustained reduction in left ventricular pressure and coronary vascular resistance. Total adenosine release fell within one minute and remained reduced during HCl. Radioactive adenosine release was elevated at 15 seconds but fell below control values at 2 minutes and remained reduced during steady-state acidosis. We conclude that the majority of the adenosine released in response to isoproterenol and acetylcholine originates from an unlabelled compartment, most likely the myocytes. Acidosis results in decreased release of adenosine from both the labelled endothelium and the unlabelled cells in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000494:pharmacology*; D000138:Acidosis / Q000378:metabolism* / Q000503:physiopathology; D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology* / Q000503:physiopathology; D006168:Guinea Pigs; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects
D000227:Adenine Nucleotides; D000241:Adenosine; D007545:Isoproterenol; D000109:Acetylcholine