Reoxygenation, but neither hypoxia nor intermittent ischemia, increases [125I]endothelin-1 binding to rat cardiac membranes.
Standard binding techniques were used to establish whether either hypoxia, reoxygenation, perfusion under acidotic conditions, or "stunning" of the myocardium resembles ischemia and postischemic reperfusion in increasing cardiac membrane [125I]endothelin-1 (ET-1) binding site density (Bmax). Membranes from aerobically perfused rat hearts bound [125I]ET-1 to a single population of sites, with an affinity (KD) of 0.093 +/- 0.004 nM and a Bmax of 98.8 +/- 5.2 fmol/mg of protein. Bmax was increased (p less than 0.01) after 30 min of global ischemia, and further increased upon reperfusion, without changes in KD or selectivity. Neither three 10 min episodes of ischemia separated by 15 min of perfusion, nor perfusion at pH 6.8 instead of 7.4, nor 60 min of hypoxia altered Bmax, KD, or selectivity. Reoxygenation after 60 min of hypoxia increased Bmax (p less than 0.01) and KD (p less than 0.01) without changing selectivity. These results are interpreted to mean that the ischemia-induced increase in Bmax for [125I]ET-1 cannot be explained simply in terms of the ischemia-induced acidosis, or the accompanying reduction in tissue adenosine triphosphate and creatine phosphate.
Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia.
J J
JJ
Liu
X H
XH
Gu
D J
DJ
Casley
W G
WG
Nayler
D000138:Acidosis / Q000378:metabolism; D000332:Aerobiosis; D000818:Animals; D015687:Cell Hypoxia; D003327:Coronary Disease / Q000378:metabolism*; D016232:Endothelins; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats
D016232:Endothelins; D007457:Iodine Radioisotopes; D010455:Peptides; D011189:Potassium Chloride