AJP - Heart and Circulatory Physiology, Vol 250, Issue 5 749-H754, Copyright © 1986 by American Physiological Society
Naloxone enhances myocardial responses to isoproterenol in dog isolated heart-lung
J. L. Caffrey, C. B. Wooldridge and J. F. Gaugl
Intracoronary injection of naloxone produces rapid local increases in
myocardial performance. The role of beta-adrenergic activation in this
response was investigated. Naloxone was injected into the left anterior
descending artery (LAD) of anesthetized dogs with the adjacent circumflex
territory serving as control. Naloxone increased the contractile state
locally in the LAD region. Pretreatment with propranolol eliminated the
regional inotropic response. An isolated heart-lung model was set up, and
isoproterenol dose responses were determined. When repeated after naloxone,
contractile (dP/dt) responses to isoproterenol were both augmented and
prolonged. In a third study imipramine was used to determine whether
naloxone might act by reducing neuronal uptake of the isoproterenol.
Imipramine extended the effect of isoproterenol temporally but did not
alter the peak response. Adding naloxone increased the peak response to
isoproterenol and maintained it above the extended imipramine response. The
data support the concept that the blockade of opiate receptors facilitates
adrenergic activity mediated by myocardial beta 1-receptors 1) directly
through postsynaptic mechanisms, 2) indirectly through beta 2-mediated
release of norepinephrine, or 3) via interference with nonneuronal disposal
mechanisms.
