Role of endogenous opioids and serotonin in the hemodynamic response to hemorrhage during acute and chronic hypoxia. Resta, Thomas C., Juanita M. Resta, and Benjimen R. Walker. Department of Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131
APStracts 2:0232H, 1995.
Previous studies from our laboratory indicate that acute but not chronic hypoxia decreases the hemorrhage volume required to elicit reflex hypotension. Furthermore, chronically hypoxic animals exhibit an elevated hypotensive threshold during both normoxia and hypoxia compared to control animals. Because reports suggest that opioid and serotonergic mechanisms may be involved in mediating the sympathoinhibition that occurs with hemorrhage, we hypothesized that opioid and/or serotonergic systems are stimulated during hemorrhage under conditions of acute hypoxia and suppressed following chronic exposure to hypoxia and are thus responsible for the altered cardiovascular responses to hemorrhage under each condition. Control and chronically hypoxic rats were administered either the opioid receptor antagonist naltrexone (1 mg_kg-1), the selective 5-HT3 serotonergic receptor antagonist MDL 72222 (0.5 mg_kg-1) or their respective vehicles intravenously prior to initiating hemorrhage during normoxia or hypoxia (FIO2= 0.12). In control animals, pretreatment with naltrexone increased the hemorrhage volume required to achieve hypotension in hypoxic but not normoxic conditions. Naltrexone had no effect on hypotensive threshold in chronically hypoxic animals under conditions of either normoxia or hypoxia. In addition, MDL 72222 had no effect on hypotensive threshold in either control or chronically hypoxic animals in either normoxic or hypoxic conditions. We conclude that endogenous opioids may contribute to the reflex hypotension that occurs during hypoxic hemorrhage in control rats, while no such involvement is evident in chronically hypoxic animals. Furthermore, peripheral 5-HT3 receptors are not likely involved in this response during either normoxic or hypoxic hemorrhage in control or chronically hypoxic rats. 

Received 19 October 1994; accepted in final form 30 May 1995.
APS Manuscript Number H935-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  6 July 1995.