© 1999 American Heart Association, Inc.
Original Contribution |
Cardioprotection of Preconditioning by Metabolic Inhibition in the Rat Ventricular Myocyte
Involvement of 
-Opioid Receptor
From the Department of Physiology and Institute of Cardiovascular Science and Medicine, Faculty of Medicine, The University of Hong Kong, China.
Correspondence to T.M. Wong, PhD, Department of Physiology, Faculty of Medicine, The University of Hong Kong, Li Shu Fan Building, Sassoon Rd, Hong Kong, China. E-mail wongtakm{at}hkucc.hku.hk
Abstract—To determine
whether opioid receptors (ORs) are involved in the delayed
cardioprotection of ischemic preconditioning (IP), the effect
of severe metabolic inhibition (MI) with a glucose-free
buffer that contained sodium cyanide and 2-deoxy-D-glucose
on the viability of isolated rat ventricular myocytes was
first determined 20 hours after preconditioning with a sublethal
metabolic inhibition (MIP) with a glucose-free buffer that
contained 2-deoxy-D-glucose and lactate for 30 minutes in
the presence of OR antagonists. With the use of trypan blue
exclusion as an index of cell viability, severe MI killed >60% of the
cells and the value increased significantly after MIP. In the presence
of 5x10-6 mol/L nor-binaltorphimine (nor-BNI), a
selective 
-OR antagonist, but not 5x10-6
mol/L CTOP, a selective µ-OR antagonist, or
5x10-6 mol/L naltrindole, a selective 
-OR
antagonist, the cardioprotection of MIP was significantly
attenuated. To verify the role of -OR, we studied the effects of
severe MI after pretreatment with the -OR agonist U50,488H (UP) for
30 minutes. U50,488H at 3x10-6 to 1x10-4
mol/L increased cell viability concentration-dependently with an
EC50 of 3.311x10-6 mol/L. In the presence of
5x10-6 nor-BNI, the cardioprotection of UP
(3x10-5 mol/L) was blocked. A time course study showed
that UP-induced cardioprotection occurred in 2 windows: the first
occurred 
1 hour later and the other occurred 16 to 20 hours later.
Additional studies on cell contraction and intracellular
Ca2+ ([Ca2+]i) revealed that both
UP and MIP attenuated the inhibitory effects of severe MI
on contractility and electrically induced
[Ca2+]i transient in single
ventricular myocytes. On blockade of protein kinase C, the
delayed cardioprotections of UP and MIP were significantly attenuated.
In conclusion, the results of the present study have provided
evidence that -OR mediates the cardioprotection of MIP, which may
involve protein kinase C and [Ca2+]i.
Key Words: receptor • contractility • Ca2+ • myocyte • protein kinase
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