The involvement of
opioid receptor activation during
ischemia-reperfusion is somewhat controversial. While it is generally accepted that activation of the
delta-opioid receptor (DOR) is cardioprotective, and may indeed be an important mediator of ischemic preconditioning, the role of the
kappa-opioid receptor (KOR) is less well understood. To this end, we examined three different KOR agonists and their effects upon
infarct size and
arrhythmia development. Male Sprague-Dawley rats were subjected to 30 minutes of occlusion followed by 90 minutes of reperfusion.
Opioid receptor agonists were administered 10 minutes before the onset of
ischemia, while the
opioid antagonists were given 20 minutes before occlusion. Untreated rats exhibited an
infarct size (IS/AAR%) of 52.4 +/- 2.7%. Pretreatment with the DOR agonist,
BW373U86, limited
infarct development to 37.2 +/- 1.8%, which was reversed by the selective DOR antagonist, BNTX. All three KOR agonists studied, U50,488, ICI 204,448, and
BRL 52537 significantly reduced
infarct size to levels comparable to that of
BW373U86. The
infarct-sparing effects of U50,488 and ICI 204,448 were abolished by the selective KOR antagonist,
nor-BNI.
Nor-BNI failed to inhibit the cardioprotective effects of
BRL 52537. Furthermore, U50,488 and
BRL 52537, but not ICI 204,448, significantly reduced the incidence of arrhythmias. These effects were not blocked by
nor-BNI. These data demonstrate that KOR activation provides a similar degree of
infarct size reduction as DOR activation. KOR agonists also reduced arrhythmogenesis; however, these responses appear to be independent of KOR activation.