Glyburide-reversible cardioprotective effects of BMS-180448: functional and energetic considerations

Journal of Cardiovascular Pharmacology
G J GroverR W Behling

Abstract

Adenosine triphosphate (ATP)-sensitive potassium channel openers as a class exert cardioprotective effects, and we can separate vasodilator from glyburide-reversible cardioprotective activity in cromakalim analogs (e.g., BMS-180448). The purpose of this study was to determine the relation between cardiac function, energy status, and cardioprotective effects for BMS-180448 in isolated rat hearts compared with diltiazem. BMS-180448 (1-30 microM) or 0.1-1 microM diltiazem were given 10 min before 25-min global ischemia in rat hearts followed by 30 min of reperfusion. Both compounds significantly increased time to the onset of contracture during ischemia and improved postischemic recovery of contractile function in a concentration-dependent manner. At equivalent cardioprotective concentrations, BMS-180448 depressed preischemic cardiac function significantly less than did diltiazem. During ischemia, diltiazem significantly accelerated the functional decline observed in vehicle-treated hearts, whereas BMS-180448 attenuated the net rate of decline of function. Despite these different effects on preischemic and ischemic cardiac function, diltiazem and BMS-180448 conserved cardiac ATP during ischemia to a similar degree. BMS-180448 enha...Continue Reading

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Citations

Oct 31, 2003·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Jonathan Rhys David CropperPeter Simon Macdonald
Apr 11, 2000·Journal of Molecular and Cellular Cardiology·G J Grover, K D Garlid
Apr 12, 2005·Journal of Cardiovascular Pharmacology·Steen B KristiansenTorsten Toftegaard Nielsen
Feb 13, 2001·American Journal of Physiology. Heart and Circulatory Physiology·A J KowaltowskiK D Garlid
Jun 14, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Pierre Dos SantosKeith D Garlid

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