Release of 6-keto-PGF1 alpha and thromboxane B2 in late appearing cardioprotection induced by the stable PGI analogue: 7-OXO-PGI.
We have shown earlier that prostacyclin (PGI2) and its stable analogue: 7-oxo-prostacyclin(7-OXO) may induce a prolonged, late appearing (24-48 h after drug administration), dose dependent protection of the heart from harmful consequences of a subsequent severe ischaemic stress, such as myocardial ischaemia, life-threatening ventricular arrhythmias and early ischaemic morphological changes. In an other study we observed that a similar but shortlived (less than 1 h) cardioprotection, induced by 'preconditioning' brief coronary artery occlusions, is greatly reduced by blockade of the cyclooxygenase pathway, suggesting that prostanoids might play a role in this shortlasting protection. Objective of our present study was to elucidate the importance of some arachidonic acid (AA) metabolites, such as PGI2 and thromboxane A2 (TXA2) in the mechanism of the late appearing, prolonged cardioprotection. Estimation of the metabolites: 6-keto-PGF1 alpha (6-KETO) and thromboxane B2 (TXB2) was made from the perfusate of isolated Langendorff hearts of guinea-pigs pretreated with 50 micrograms/kg 7-OXO, 24 and 48 h before preparation. Pretreatment alone produced a slight, but significant elevation of 6-KETO (from 206 +/- 11 to 284 +/- 19 pg/ml/min after 24 h, and to 261 +/- 18 pg/ml/min after 48 h). No change was seen in TXB2 production. Global ischaemia for 25 min (followed by 25 min reperfusion) markedly increased the release of both AA metabolites; maximal values were observed in the third min of reperfusion (6-KETO from 206 +/- 11 to 1275 +/- 55 pg/ml/min and TXB2 from 29 +/- 4 to 172 +/- 12 pg/ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)
Szekeres
L
L
Institute of Pharmacology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Tósaki
A
A
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000818:Animals; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000517:prevention & control; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism*
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C033705:7-oxoprostaglandin I2; D011464:Epoprostenol