Abstract
1. We have tested the hypothesis that the pressor action of (-) naloxone HC1 after haemorrhage is due to antagonism of endogenous opiate mechanisms that are activated by haemorrhage, rather than to some more direct vasoconstrictor action of the drug. 2. Six conscious rabbits were treated intravenously with either naloxone (4 mg kg-1, then 0.1 mg kg-1 min-1) or equivalent volumes of saline. In unbled rabbits the naloxone regimen had no effect except to cause a transient bradycardia. After each treatment the rabbits were bled at a rate of 2.45 ml kg-1 min-1 until blood pressure fell to 40 mmHg or 28 ml kg-1 of blood had been withdrawn (17-24 ml kg-1 after saline, 21-28 ml kg-1 after naloxone). 3. Throughout both episodes of bleeding there was a progressive fall of cardiac output and rise of heart rate, at rates that were constant and independent of the prior treatment. 4. After saline treatment, bleeding at first resulted in a steep and progressive fall of systemic vascular conductance and a small fall in blood pressure. However, when blood loss exceeded 12.7 ml kg-1 (approximately 28% of blood volume) there was an abrupt rise in systemic vascular conductance and an abrupt fall in blood pressure. 5. After naloxone treatment, during the entire period of bleeding systemic vascular conductance fell steeply and blood pressure fell slowly. 6. The different effects of saline and naloxone on the haemodynamic responses to acute blood loss were not explicable by differences in haematocrit or net blood volume. 7. We conclude that endogenous opiate mechanisms are responsible for the abrupt vasodilation that occurs when more than 28% of blood volume is withdrawn rapidly from conscious rabbits. We suggest that these mechanisms reside in the central nervous system.
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Selected References
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- Atweh S. F., Kuhar M. J. Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla. Brain Res. 1977 Mar 18;124(1):53–67. doi: 10.1016/0006-8993(77)90863-0. [DOI] [PubMed] [Google Scholar]
- Chalmers J. P., Korner P. I., White S. W. Effects of haemorrhage on the distribution of the peripheral blood flow in the rabbit. J Physiol. 1967 Sep;192(2):561–574. doi: 10.1113/jphysiol.1967.sp008317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chalmers J. P., Korner P. I., White S. W. The effects of haemorrhage in the unanaesthetized rabbit. J Physiol. 1967 Apr;189(3):367–391. doi: 10.1113/jphysiol.1967.sp008174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dashwood M. R., Gilbey M. P., Spyer K. M. The localization of adrenoceptors and opiate receptors in regions of the cat central nervous system involved in cardiovascular control. Neuroscience. 1985 Jun;15(2):537–551. doi: 10.1016/0306-4522(85)90232-5. [DOI] [PubMed] [Google Scholar]
- Faris I. B., Iannos J., Jamieson G. G., Ludbrook J. The circulatory effects of acute hypervolemia and hemodilution in conscious rabbits. Circ Res. 1981 Jun;48(6 Pt 1):825–834. doi: 10.1161/01.res.48.6.825. [DOI] [PubMed] [Google Scholar]
- Holaday J. W. Cardiovascular effects of endogenous opiate systems. Annu Rev Pharmacol Toxicol. 1983;23:541–594. doi: 10.1146/annurev.pa.23.040183.002545. [DOI] [PubMed] [Google Scholar]
- Joseph S. A., Pilcher W. H., Bennett-Clarke C. Immunocytochemical localization of ACTH perikarya in nucleus tractus solitarius: evidence for a second opiocortin neuronal system. Neurosci Lett. 1983 Aug 8;38(3):221–225. doi: 10.1016/0304-3940(83)90372-5. [DOI] [PubMed] [Google Scholar]
- Ludbrook J., Graham W. F. The role of cardiac receptor and arterial baroreceptor reflexes in control of the circulation during acute change of blood volume in the conscious rabbit. Circ Res. 1984 Apr;54(4):424–435. doi: 10.1161/01.res.54.4.424. [DOI] [PubMed] [Google Scholar]
- Maley B., Elde R. Immunohistochemical localization of putative neurotransmitters within the feline nucleus tractus solitarii. Neuroscience. 1982 Oct;7(10):2469–2490. doi: 10.1016/0306-4522(82)90208-1. [DOI] [PubMed] [Google Scholar]
- Morita H., Vatner S. F. Effects of hemorrhage on renal nerve activity in conscious dogs. Circ Res. 1985 Nov;57(5):788–793. doi: 10.1161/01.res.57.5.788. [DOI] [PubMed] [Google Scholar]
- Månsson J., Skoog P., Thorén P. Naloxone and haemorrhagic hypotension in rats. Evidence against sympathetic nervous system as the primary mediator of improved cardiovascular haemodynamics. Acta Physiol Scand. 1986 Jun;127(2):155–159. doi: 10.1111/j.1748-1716.1986.tb07888.x. [DOI] [PubMed] [Google Scholar]
- Paterson S. J., Robson L. E., Kosterlitz H. W. Classification of opioid receptors. Br Med Bull. 1983 Jan;39(1):31–36. doi: 10.1093/oxfordjournals.bmb.a071787. [DOI] [PubMed] [Google Scholar]
- Rutter P. C., Pavia J. M., Ludbrook J. Analysis of mechanisms responsible for the bradycardic action of naloxone after haemorrhage in the conscious rabbit. J Auton Nerv Syst. 1987 Feb;18(2):131–141. doi: 10.1016/0165-1838(87)90100-7. [DOI] [PubMed] [Google Scholar]
- Rutter P. C., Potocnik S. J., Ludbrook J. Factors influencing the effects of intravenous naloxone on arterial pressure and heart rate after haemorrhage in conscious rabbits. Clin Exp Pharmacol Physiol. 1986 May;13(5):383–397. doi: 10.1111/j.1440-1681.1986.tb00917.x. [DOI] [PubMed] [Google Scholar]
- Schadt J. C., Gaddis R. R. Cardiovascular responses to hemorrhage and naloxone in conscious barodenervated rabbits. Am J Physiol. 1986 Nov;251(5 Pt 2):R909–R915. doi: 10.1152/ajpregu.1986.251.5.R909. [DOI] [PubMed] [Google Scholar]
- Schadt J. C., Gaddis R. R. Endogenous opiate peptides may limit norepinephrine release during hemorrhage. J Pharmacol Exp Ther. 1985 Mar;232(3):656–660. [PubMed] [Google Scholar]
- Schadt J. C., McKown M. D., McKown D. P., Franklin D. Hemodynamic effects of hemorrhage and subsequent naloxone treatment in conscious rabbits. Am J Physiol. 1984 Sep;247(3 Pt 2):R497–R505. doi: 10.1152/ajpregu.1984.247.3.R497. [DOI] [PubMed] [Google Scholar]
- Schadt J. C., York D. H. The reversal of hemorrhagic hypotension by naloxone in conscious rabbits. Can J Physiol Pharmacol. 1981 Dec;59(12):1208–1213. doi: 10.1139/y81-189. [DOI] [PubMed] [Google Scholar]
- Skoog P., Månsson J., Thorén P. Changes in renal sympathetic outflow during hypotensive haemorrhage in rats. Acta Physiol Scand. 1985 Dec;125(4):655–660. doi: 10.1111/j.1748-1716.1985.tb07768.x. [DOI] [PubMed] [Google Scholar]
- Warren J. V., Brannon E. S., Stead E. A., Merrill A. J. THE EFFECT OF VENESECTION AND THE POOLING OF BLOOD IN THE EXTREMITIES ON THE ATRIAL PRESSURE AND CARDIAC OUTPUT IN NORMAL SUBJECTS WITH OBSERVATIONS ON ACUTE CIRCULATORY COLLAPSE IN THREE INSTANCES. J Clin Invest. 1945 May;24(3):337–344. doi: 10.1172/JCI101611. [DOI] [PMC free article] [PubMed] [Google Scholar]