COX-2-dependent and potentially cardioprotective effects of negative inotropic substances released after ischemia

Item Type:	Article
Title:	COX-2-dependent and potentially cardioprotective effects of negative inotropic substances released after ischemia
Creators Name:	Birkenmeier, K. and Staudt, A. and Schunck, W.H. and Janke, I. and Labitzke, C. and Prange, T. and Trimpert, C. and Krieg, T. and Landsberger, M. and Stangl, V. and Felix, S.B.
Abstract:	During reperfusion, cardiodepressive factors are released from isolated rat hearts after ischemia. The present study analyzes the mechanisms by which these substances mediate their cardiodepressive effect. After 10 min of global stop-flow ischemia, rat hearts were reperfused and coronary effluent was collected over a period of 30 s. We tested the effect of this postischemic effluent on systolic cell shortening and Ca(2+) metabolism by application of fluorescence microscopy of field-stimulated rat cardiomyocytes stained with fura-2 AM. Cells were preincubated with various inhibitors, e.g., the cyclooxygenase (COX) inhibitor indomethacin, the COX-2 inhibitors NS-398 and lumiracoxib, the COX-1 inhibitor SC-560, and the potassium (ATP) channel blocker glibenclamide. Lysates of cardiomyocytes and extracts from whole rat hearts were tested for expression of COX-2 with Western blot analysis. As a result, in contrast to nonischemic effluent (control), postischemic effluent induced a reduction of Ca(2+) transient and systolic cell shortening in the rat cardiomyocytes (P < 0.001 vs. control). After preincubation of cells with indomethacin, NS-398, and lumiracoxib, the negative inotropic effect was attenuated. SC-560 did not influence the effect of postischemic effluent. The inducibly expressed COX-2 was detected in cardiomyocytes prepared for fluorescence microscopy. The effect of postischemic effluent was eliminated with applications of glibenclamide. Furthermore, postischemic effluent significantly reduced the intracellular diastolic and systolic Ca(2+) increase (P < 0.01 vs. control). In conclusion, the cardiodepressive effect of postischemic effluent is COX-2 dependent and protective against Ca(2+) overload in the cells.
Keywords:	Cyclooxygenase, Potassium Adenosine 5'-Triphosphate Channels, Animals, Rats
Source:	American Journal of Physiology: Heart and Circulatory Physiology
ISSN:	0363-6135
Publisher:	American Physiological Society
Volume:	293
Number:	4
Page Range:	H2148-H2154
Date:	1 October 2007
Official Publication:	https://doi.org/10.1152/ajpheart.00074.2007
PubMed:	View item in PubMed

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