Inositol phosphate release and metabolism during myocardial ischemia and reperfusion in rat heart.
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| Abstract |
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.
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| Authors | K E Anderson, A M Dart, E A Woodcock |
| Journal | Circulation research (Circ Res) Vol. 76 Issue 2 Pg. 261-8 (Feb 1995) ISSN: 0009-7330 [Print] United States |
| PMID | 7834837 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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