Activation of kappa-opioid receptors in the nucleus ambiguus does not affect cardiovascular function or outcome following acute hemorrhage in the rat.
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.
Samuels
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Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104.
McIntosh
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D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage / Q000503:physiopathology*; D007022:Hypotension / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*
D017473:Receptors, Opioid, kappa