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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.
Br J Pharmacol. 1999 Feb; 126(4):849-58.BJ

Abstract

1. 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. 2. 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. 3. M&B 28767 (0.5 microg kg(-1) min(-1), i.v., n=7) or GR 63799X (3 microg 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. 4. 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.

Authors+Show Affiliations

The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, England, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10193764

Citation

Zacharowski, K, et al. "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." British Journal of Pharmacology, vol. 126, no. 4, 1999, pp. 849-58.
Zacharowski K, Olbrich A, Otto M, et al. 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. Br J Pharmacol. 1999;126(4):849-58.
Zacharowski, K., Olbrich, A., Otto, M., Hafner, G., & Thiemermann, C. (1999). 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. British Journal of Pharmacology, 126(4), 849-58.
Zacharowski K, et al. 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. Br J Pharmacol. 1999;126(4):849-58. PubMed PMID: 10193764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Zacharowski,K, AU - Olbrich,A, AU - Otto,M, AU - Hafner,G, AU - Thiemermann,C, PY - 1999/4/8/pubmed PY - 1999/4/8/medline PY - 1999/4/8/entrez SP - 849 EP - 58 JF - British journal of pharmacology JO - Br J Pharmacol VL - 126 IS - 4 N2 - 1. 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. 2. 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. 3. M&B 28767 (0.5 microg kg(-1) min(-1), i.v., n=7) or GR 63799X (3 microg 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. 4. 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/10193764/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_ L2 - https://doi.org/10.1038/sj.bjp.0702348 DB - PRIME DP - Unbound Medicine ER -