Cellular source and role of adenosine in isoproterenol-induced coronary vasodilatation.
The role of adenosine and its cellular source in isoproterenol-induced coronary vasodilatation was investigated in isolated perfused rat hearts prelabelled with [3H]adenosine. Time courses (times for half-maximal increase) were measured for changes in oxygen consumption (2.23 +/- 0.22 min), coronary flow (3.30 +/- 0.33 min), concentrations of effluent radioactivity (3.92 +/- 0.30 min) and adenosine and its metabolites (inosine, hypoxanthine and xanthine) (2.00 +/- 0.23 min). Isoproterenol stimulation decreased the cellular energy state and increased the concentration of tissue adenosine and its metabolites. Coronary flow was linearly correlated with tissue adenosine (r = 0.85) and phosphorylation potential (r = -0.82) and tissue adenosine also showed a linear correlation with phosphorylation potential (r = -0.84) and tissue free [AMP] (r = 0.79). The specific radioactivities of tissue nucleotides remained constant, but those of adenosine, inosine and hypoxanthine + xanthine were decreased by 42%, 26% and 46%, respectively. Purine compound concentrations increased during isoproterenol stimulation from basal values of 56 +/- 23, 98 +/- 33 and 44 +/- 19 nM to 388 +/- 173, 583 +/- 156 and 178 +/- 27 nM, respectively. The basal specific radioactivity ratio of adenosine:inosine:(hypoxanthine + xanthine) in the effluent perfusate was 1:0.5:7, but the specific radioactivities decreased rapidly upon isoproterenol stimulation, and at 3 min the ratio had changed to 1:2.5:16.5. The time courses of release and the changes in the specific radioactivities of the nucleosides indicate that adenosine release occurred mainly from cardiomyocytes, and that the release of adenosine and its metabolites from the cardiomyocytes preceded that from the endothelium. It is also shown that adenosine release during catecholamine stimulation occurs concomitantly with a decrease in the cellular energy state and AMP accumulation. This is in accord with the adenosine hypothesis of coronary vasoregulation.
Pekka Raatikainen
M J
MJ
Department of Medical Biochemistry, University of Oulu, Finland.
Peuhkurinen
K J
KJ
Hassinen
I E
IE
D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D019820:Xanthine; D014970:Xanthines / Q000378:metabolism
D007042:Hypoxanthines; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine; D007288:Inosine; D000255:Adenosine Triphosphate; D000241:Adenosine; D007545:Isoproterenol