The central cardiovascular response to
hemorrhage is believed to be regulated, in part, by specific brain cardioregulatory nuclei, including the nucleus ambiguus (NA) of the hindbrain. Since endogenous
opioid peptides and
opiate receptors have been localized to this brain region, activation of endogenous
opioid systems in the NA may affect the cardiovascular response to acute
hemorrhage. The present study examined the effects of intracerebral microinjection of
kappa-receptor agonists into the NA prior to acute fixed-volume
hemorrhage in awake rats. 15 min prior to fixed volume
hemorrhage (7.5 ml/300 g), male Sprague-Dawley rats (n = 59) received a microinjection of either (1) the synthetic
kappa-receptor agonist
U-50,488H (10 nM) or (2)
U-50,488H (100 nM) or (3) the endogenous
kappa-receptor agonist
dynorphin 1-17 (1 nM) or (4) Des-Tyr
dynorphin 2-17, inactive at
opiate receptors (1 nM) or (5) equal volume saline. With the exception of the first 10 min post-
hemorrhage, where intracerebral injection of both
dynorphin 1-17 and
dynorphin 2-17 caused a transient suppression of mean arterial blood pressure (P < 0.05 when compared to saline-treated controls), microinjection of the kappa-agonists
dynorphin 1-17 or
U-50,488H had no effect on blood pressure, heart rate or mortality when compared to control animals. These results suggest that activation of kappa-
opiate receptors in the NA does not markedly influence cardiovascular response to acute
hemorrhage.