NDLI: Effects of the prostanoid EP3-receptor agonists M&B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat

Content Provider	PubMed Central
Author	Kai, Zacharowski Olbrich, Antje Otto, Mike Hafner, Gerd Christoph, Thiemermann
Copyright Year	1999
Abstract	This study investigates the effects of two agonists of the prostanoid EP3-receptor (M&B 28767 and GR 63799X) on the infarct size caused by regional myocardial ischaemia and reperfusion in the anaesthetized rat. One hundred and sixty-seven, male Wistar rats were anaesthetized (thiopentone, 120 mg kg−1, i.p.), ventilated (8–10 ml kg−1, 70 strokes min−1, inspiratory oxygen concentration: 30%; PEEP: 1–2 mmHg) and subjected to occlusion of the left anterior descending coronary artery (LAD, for 7.5, 15, 25, 35, 45 or 60 min) followed by reperfusion (2 h). Infarct size was determined by staining of viable myocardium with a tetrazolium stain (NBT), histological evaluation by light and electron microscopy and determination of the plasma levels of cardiac troponin T. M&B 28767 (0.5 μg kg−1 min−1, i.v., n=7) or GR 63799X (3 μg kg−1 min−1, i.v., n=7) caused significant reductions in infarct size from 60±3% (25 min ischaemia and 2 h reperfusion; saline-control, n=8) to 39±6 and 38±4% of the area at risk, without causing a significant fall in blood pressure. Pretreatment of rats with 5-hydroxydecanoate (5-HD), an inhibitor of ATP-sensitive potassium channels, attenuated the cardioprotective effects of both EP3-receptor agonists. The reduction in infarct size afforded by M&B 28767 was also abolished by glibenclamide and the protein kinase C (PKC) inhibitors staurosporine and chelerythrine. Thus, M&B 28767 and GR 63799X reduce myocardial infarct size in the rat by a mechanism(s) which involves the activation of PKC and the opening of ATP-sensitive potassium channels.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0702348
Ending Page	858
Page Count	10
Starting Page	849
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	4
Volume Number	126
Language	English
Publisher Date	1999-02-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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