AJP - Heart and Circulatory Physiology, Vol 256, Issue 5 1353-H1360, Copyright © 1989 by American Physiological Society
Diabetes alters postischemic response to a prostacyclin mimetic
G. M. Pieper and G. J. Gross
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
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.
