Myocardial adenosine formation during hypoxia: effects of ecto-5'-nucleotidase inhibition.
Release of adenosine and AMP into epicardial fluid and coronary venous effluent of isovolumic guinea-pig hearts was examined during normoxic (95% O2) and hypoxic (30% O2) perfusion with and without the ecto-5'-nucleotidase inhibitor alpha,beta-methylene adenosine diphosphate (AOPCP)*. Normoxic epicardial and venous adenosine levels were 221 +/- 27 and 67 +/- 11 nM, respectively, in untreated hearts. During 15 min of hypoxia, epicardial and venous adenosine levels increased in a phasic manner, reaching maximal values of 498 +/- 32 and 441 +/- 43 nM, respectively, during the initial 5 min of hypoxia. Epicardial and venous adenosine levels then declined slightly during the subsequent 10 min to 332 +/- 33 and 224 +/- 34 nM, respectively. Infusion of 50 microM AOPCP significantly reduced venous adenosine levels during normoxia (less than 50% of control), but was without effect on normoxic epicardial adenosine. Epicardial and venous adenosine levels increased during hypoxia with AOPCP but the increases were lower than those for untreated hypoxic hearts. Epicardial and venous adenosine levels recovered to baseline levels following 30 min of reoxygenation in both groups. Epicardial and venous AMP levels were elevated by AOPCP treatment during normoxia and hypoxia. Coronary vascular resistance decreased during hypoxia but the decline in resistance was less in AOPCP treated hearts. It is concluded that whereas basal interstitial adenosine levels appear to be independent of ecto-5'-nucleotidase activity, the hypoxic increase in interstitial adenosine is partially derived from an AOPCP sensitive ecto-5'-nucleotidase. Venous adenosine appears to be significantly dependent on ecto-5'-nucleotidase activity during normoxia and hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Headrick
J P
JP
Department of Physiology, Health Sciences Center, University of Virginia, Charlottesville 22908.
Matherne
G P
GP
Berne
R M
RM
D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors*; D000241:Adenosine / Q000096:biosynthesis*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D015720:5'-Nucleotidase; D000241:Adenosine