Inositol phosphate release and metabolism during myocardial ischemia and reperfusion in rat heart.
A detailed study of the effects of global myocardial ischemia and reperfusion on inositol phosphate release and metabolism has been undertaken by using isolated perfused rat hearts. Ischemia for longer than 5 minutes caused a cessation of inositol phosphate production, with inositol phosphates initially present accumulating as isomers of inositol monophosphate. This inhibition was independent of norepinephrine. In contrast, 2-minute reperfusion following 20-minute ischemia produced a rapid and transient release of inositol phosphates that was dependent on the release of norepinephrine and mediated by alpha 1-adrenergic receptors. By a number of criteria, this reperfusion response was different from the norepinephrine response in normoxic tissue. First, total release of inositol phosphates was greater (466 +/- 37 compared with 345 +/- 29 cpm/mg protein, P < .05). Second, inositol 1,4,5-trisphosphate was released with postischemic reperfusion (103 +/- 18 to 207 +/- 11 pmol/mg protein), whereas release was not detected in normoxic myocardium. In agreement with this, neomycin (0.5 and 5 mmol/L) inhibited inositol phosphate release only under reperfusion conditions. Third, the reperfusion response, unlike the response in nonischemic tissue, required extracellular Ca2+. Longer periods of reperfusion resulted in a return to a pattern of inositol phosphate release that was not different from that seen in normoxic tissue. The rapid and transient release of inositol 1,4,5-trisphosphate at 2-minute postischemic reperfusion provides an explanation for the enhanced role of alpha 1-adrenergic receptors under these conditions and suggests an important role for this compound in initiating reperfusion-induced pathological events.
Cellular Biochemistry Laboratory, Baker Medical Research Institute, Prahran, Australia.
K E
KE
Anderson
A M
AM
Dart
E A
EA
Woodcock
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D007295:Inositol Phosphates; D009355:Neomycin; D002118:Calcium; D009638:Norepinephrine