Previous work from this laboratory has demonstrated that
opioid peptides, acting at
mu-receptors in the brain, stimulate central sympathetic outflow thereby increasing plasma
catecholamine concentrations in unstressed rats. Brain sites involved in
opioid-mediated
catecholamine secretion have not been characterized fully. Additionally, brain
opioid effects on sympathoadrenal
catecholamine secretion during stress have not been defined. Because the paraventricular hypothalamic nucleus (PVN) plays a central role in autonomic and cardiovascular regulation, we administered the mu-selective
enkephalin analog, D-Ala2-NMe-Phe4-Gly(ol)5enkephalin (
DAGO), directly into PVN in conscious, unstressed rats and determined the changes in plasma
catecholamine concentrations, blood pressure and heart rate. Then, during the peak response, rats were subjected to restraint stress and the same parameters were again measured. Under basal conditions, picomolar doses of
DAGO injected into PVN increased plasma concentrations of
catecholamines, especially
epinephrine, and raised blood pressure. These effects were dose-related (0.01-0.3 nmol) and antagonized by
naloxone given either systemically or directly into PVN.
Tachycardia was also observed except at the highest dose of
DAGO (0.3 nmol). Thus,
mu-receptor stimulation in PVN increases central sympathetic outflow in nonstressful situations, producing increased adreno-medullary
catecholamine secretion, blood pressure and heart rate. During restraint stress, PVN microinjections of
DAGO blunted stress-induced
tachycardia, apparently by a vagal mechanism as this effect was blocked by
atropine methyl nitrate. PVN
DAGO had no significant effect on the plasma
catecholamine responses to restraint stress. In contrast,
naloxone injected into PVN augmented stress-induced
epinephrine secretion. Thus, PVN
mu-receptors may regulate heart rate during stress, and an endogenous
opioid released during restraint stress may modulate adrenomedullary responses to stress.