S. Cavun et al., Blockade of delta opioid receptors in the ventrolateral periaqueductal gray region inhibits the fall in arterial pressure evoked by hemorrhage, J PHARM EXP, 297(2), 2001, pp. 612-619
Citations number
40
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Severe hemorrhage lowers arterial pressure by suppressing sympathetic activ
ity. The central mechanism that initially triggers the fall in arterial pre
ssure evoked by hemorrhage is not well understood, although opioid neurons
are thought to play a role. This study tested the hypothesis that hemorrhag
ic hypotension is mediated by delta opioid receptors in the ventrolateral p
eriaqueductal gray (vlAG), a region importantly involved in opioid analgesi
a. Depressor sites were first identified by microinjecting DL-homocysteic a
cid (20 nmol/0.1 mul) or beta -endorphin (0.5 nmol/0.1 mul) into the vlPAG
of halothane-anesthetized rats. Consistent with earlier reports, DL-homocys
teic acid injection into the caudal vlPAG lowered arterial pressure and hea
rt rate; beta -endorphin evoked a comparable depressor response, but did no
t affect heart rate. Naloxone or selective opioid receptor antagonists were
subsequently injected into the vlPAG 5 min before hemorrhage (1.9 or 2.5 m
l/100 g of body weight over 20 min) was initiated using the same stereotaxi
c coordinates. Naloxone injection into the caudal vlPAG completely prevente
d the fall in arterial pressure evoked by hemorrhage. The response was dose
-dependent and evident with both fixed volume and fixed pressure hemorrhage
. The delta opioid receptor antagonist naltrindole inhibited hemorrhagic hy
potension significantly in both conscious and anesthetized rats but mu and
kappa receptor antagonists were ineffective. beta -Endorphin(1-27), an endo
genous opioid receptor antagonist, was also significantly inhibitory. Naltr
indole was ineffective when injected into the dorsolateral periaqueductal g
ray and did not influence cardiovascular function in nonhemorrhaged animals
. These data support the hypothesis that hemorrhagic hypotension is mediate
d by delta opioid receptors in the vlPAG.