Diabetes alters postischemic response to a prostacyclin mimetic.
Eicosanoid metabolism is altered by diabetes. However, postischemic responses of diabetic hearts (DH) to eicosanoids such as prostacyclin are unknown. a prostacyclin analogue iloprost (Ilo) was given to isovolumically beating rat hearts during 20 min of total global ischemia and 30 min of reperfusion. Acute DH (48 h) but not chronic DH (2 mo) had pronounced postischemic dysfunction (developed pressure = 22 +/- 11%), which was completely reversed by 3 X 10(-8) M Ilo (developed pressure = 113 +/- 15%). Ilo also stimulated endogenous prostacyclin release in postischemic control hearts (CH) but not acute or chronic DH. Ilo significantly decreased postischemic recovery in CH (from 67 +/- 11 to 15 +/- 4%), which was partially blocked by the coadministration of the calcium-entry blocker diltiazem or almost completely reversed by the free radical scavengers superoxide dismutase plus catalase (100 U/ml). These data suggest that Ilo may promote functional recovery in DH at concentrations that produce dysfunction in CH. Furthermore, Ilo may induce dysfunction in CH by a calcium ionophoretic action, which appears depressed in diabetes, and by concomitant free radical production (presumably via prostaglandin hydroperoxidases) during Ilo-stimulated endogenous prostacyclin synthesis.
Pieper
G M
GM
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Gross
G J
GJ
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D011464:Epoprostenol / Q000009:adverse effects / Q000096:biosynthesis / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D016285:Iloprost; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D011465:Prostaglandins, Synthetic; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D011465:Prostaglandins, Synthetic; D011464:Epoprostenol; D016285:Iloprost