From the Department of Pharmacology and Toxicology, Medical College of
Wisconsin, Milwaukee.
Correspondence to Garrett J. Gross, PhD, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226.
Background—Our laboratory has
previously shown that
Methods and Results—Anesthetized, open chest, male Wistar
rats were assigned to 1 of 14 groups. All animals were subjected to 30
minutes of occlusion and 2 hours of reperfusion. Ischemic
preconditioning was elicited by three 5-minute occlusion periods
interspersed with 5 minutes of reperfusion. Two doses of
7-benzylidenenaltrexone (BNTX; 1 and 3 mg/kg IV), a selective
Conclusions—These results indicate that
© 1998 American Heart Association, Inc.
Basic Science Reports
Ischemic Preconditioning in the Intact Rat Heart Is Mediated by
1- But Not µ- or 
-Opioid Receptors
-opioid receptors are involved in the
cardioprotective effect of ischemic preconditioning in the rat
heart. However, this class of receptors consists of two subtypes,
1 and 2, and µ- or -opioid
receptors may also exist in the heart. Therefore, the purpose of the
present study was to test the hypothesis that ischemic
preconditioning is mediated through stimulation of one or both
-opioid receptor subtypes. 1-opioid receptor antagonist, or naltriben
(NTB; 1 and 3 mg/kg IV), a selective 2-opioid receptor
antagonist, were given before ischemic
preconditioning. To test for a role of µ-opioid receptors, rats were
pretreated with ß-funaltrexamine (ß-FNA; 15 mg/kg SC), an
irreversible µ-opioid receptor antagonist, 24 hours
before ischemic preconditioning or given the µ-opioid
receptor agonist
D-Ala,2N-Me-Phe,4glycerol5-enkephalin
(DAMGO) as three 5-minute infusions (1, 10, and 100 µg/kg per
infusion IV, respectively) interspersed with 5-minute drug-free periods
before the prolonged ischemic and reperfusion periods
(lowDAMGO, medDAMGO, and hiDAMGO, respectively). The involvement of
-opioid receptors was tested by administering one of two doses of
nor-binaltorphimine (nor-BNI; 1 and 5
mg/kg IV) before ischemic preconditioning. Infarct size (IS) as
a percent of the area at risk (AAR) was measured by
triphenyltetrazolium stain.
Ischemic preconditioning markedly reduced IS/AAR (14±4%,
P<.05) compared with control (55±4%). NTB, ß-FNA,
and nor-BNI were unable to block the cardioprotective
effect of ischemic preconditioning. In addition, DAMGO had no
effect on IS/AAR. However, the high dose of BNTX (3 mg/kg IV)
significantly attenuated the cardioprotective effect of
ischemic preconditioning (39±5%; P<.05 versus
control and ischemic preconditioning). 1-opioid
receptors play an important role in the cardioprotective effect of
ischemic preconditioning in the rat heart.
Key Words: receptors • ischemia • myocardial infarction • signal transduction • heart diseases
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