Summary
The contribution of exogenous and endogenous opioid peptides to the central modulation of the baroreceptor reflex was investigated in rabbits.
Baroreceptor sensitivity was assessed in pentobarbitone anaesthetised animals by measuring heart period in response to rises in arterial pressure after bolus intravenous injections of phenylephrine and falls induced by intravenous sodium nitroprusside and controlled haemorrhage. The slope of the linear relationship between arterial pressure and heart period was used as an index of baroreflex sensitivity.
Thirty minutes after the intracisternal administration of 50 μg/kg RX783016 (a μ-opiate receptor agonist) baroreceptor sensitivity was reduced to all three methods of blood pressure manipulation. Ketazocine (50 μg/kg) a κ-opiate agonist and [d-Ala 2, d-Leu 5] enkephalin (1 μg/kg) a δ-opiate agonist, 15 min after intracisternal injection caused an increase in baroreflex sensitivity in response to a rise in pressure and a reduction in response to a fall.
Intravenous injection of naloxone (80 μg/kg) caused an increase in varoreflex gain. However, a higher dose (200 μg/kg) was required to attenuate the effects of RX783016 and [d-Ala 2, d-Leu 5] enkephalin but not ketazocine. No change in baseline arterial pressure or heart rate occurred after the opiates or naloxone. It appears that exogenous and endogenous opiates modify baroreceptor reflex function, through a mechanism which involves central opiate receptors of the μ- and κ-types.
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References
Atweh SF, Kuhar MJ (1977) Autoradiograph localisation of opiate receptors in rat brain; 1. Spinal cord and lower medulla. Brain Res 124:53–67
Beubler E (1980) Naloxone increases carbon dioxide stimulated respiration in the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 311:199–203
Bolme P, Fuxe K, Agnati R, Bradley R, Smythies J (1978) Cardiovascular effects of morphine and opioid peptides following intracisternal administration in chloralose anaesthetised rats. Eur J Pharmacol 48:319–324
Bower JD, Handa BK, Lane AC, Lord JAH, Metcalfe G, Morgan BA, Rance MJ, Richards PM, Smith CFC (1980) Structure function studies in peptides related to the — LPH 61-64 sequence In: Way EL (ed) Endogenous and exogenous opiate agonists and antagonists. Pergamon Press, New York, p 29
Chalmers JC, Reid JL (1972) Participation of central noradrenergic neurones in arterial baroreceptor reflexes in the rabbit. Circ Res 36:789–804
Chang KJ, Cuatrecasas (1979) Multiple opiate receptors. Enkepahlins and morphines bind to receptors of different specificity. J Biol Chem 254:2610–2618
Clark WG (1979) Influence of opioids on central thermoregulatory mechanisms. Pharmacol Biochem Behav 10:609–613
Elde R, Hökfelt T, Johansson O, Ljungdahl P, Nilsson G, Jeffcoate SL (1978) Immunohistochemical localization of peptides in the nervous system. In: Hughes J (ed) Centrally Acting Peptides. The MacMillan Press, London, pp 17–35
Faden AI, Holaday JW (1979) Opiate antagonists: A role in the treatment of hypovolemic shock. Science 205:317–318
Faden AI, Holaday JW (1980) Naloxone treatment of endotoxin shock: stereospecificity of physiologic and pharmacologic effects in the rat. J Pharmacol Exp Ther 212:441–447
Feldberg W, Wei E (1978) Central cardiovascular effects of enkephalins and C-fragment of lipotropin. J Physiol 280:18P
Gilbert PE, Martin WR (1976) The effects of morphine and nalorphine-like drugs in the non-dependent, morphine-dependent and cyclazocine-dependent spinal dog. J Pharmacol Exp Ther 198:66–82
Handa BK, Lane AC, Lord JAH, Morgan BA, Rance MJ, Smith CFC (1981) Analogues of β-LPH 61–64 possessing selective agonist activity at μ-opiate receptors. Eur J Pharmacol 70:531–540
Janssen HF, Lutherer LO (1980) Ventriculo cisternal administration of naloxone protects against severe hypotension during shock. Brain Res 194:608–612
Kosterlitz HW, Hughes J (1975) Some thoughts on the significance of enkephalin, the endogenous ligand. Life Sci 17:91–96
Kosterlitz HW, Paterson SJ, Robson LE (1981) Characterization of the κ-subtype of the opiate receptor in the guinea pig brain. Br J Pharmacol 73:939–949
Kosterlitz HW, Lord JA, Paterson SJ, Waterfield AA (1980) Effects of changes in the structure of enkephalins and of narcotic analgesic drugs in their interactions with μ- and δ-receptors. Br J Pharmacol 68:333–342
Laubie M, Schmitt H (1981) Indication for central vagal endorphinergic control of heart rate in dogs. Eur J Pharmacol 71:401–409
Laubie M, Schmitt H, Drouillat M (1977a) Central sites and mechanisms of the hypotensive and bradycardia effects of the narcotic analgesic agent fentanyl. Naunyn-Schmiedeberg's Arch Pharmacol 296:255–261
Laubie M, Schmitt H, Vincent M, Remona G (1977b) Central cardiovascular effects of morphinomimetic peptides in dogs. Eur J Pharmacol 46:67–71
Lord JAH, Waterfield AA, Hughes T, Kosterlitz HW (1977) Endogenous opioid peptides: multiple agonists and receptors. Nature 267:495–499
MacKenzie JE, McGrath JC, Tetrault JP, Millar RA (1976) The effects of althesin and thiopentone on sympathetic and baroreflex activity. Can Anaesth Soc J 23:252–262
Mancia G, Ludbrook J, Ferrari A, Gregorini L, Zanchetti A (1978) Baroreceptor reflexes in human hypertension. Circ Res 43:170–177
Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE (1976) The effects of morphine and nalorphine-like drugs in the non-dependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 197:517–532
Neter J, Wasserman W (1974) Applied Linear Statistical Models. Richard D Irwin Inc, Homewood, Illinois
Oka T, Negishi K, Suda M, Matsumiya T, Inazu T, Ueko M (1981) Rabbit vas deferens: A specific bioassay for opioid κ-receptor agonists. Eur J Pharmacol 73:235–236
Palkovits M, Zaborsky L (1977) Neuroanatomy of central cardiovascular control in hypertension and brain mechanisms. In: de Jong W, Provoost AP, Shapira AP (eds) Progress in Brain Research vol 47. Elsevier Scientific Publishing Co, Amsterdam pp 9–34
Petty MA, Reid JL (1981) Captopril and baroreceptor reflex responses to pressor and depressor stimuli in the rabbit. J Auton Pharmacol 1:211–215
Ramabadran K, Jacob JJC (1979) Stereospecific effects of opiate antagonists on superficial and deep nociception and on motor activity suggests involvement of endorphins on different opioid receptors. Life Sci 24:1959–1970
Sawynok J, Pinsky C, La Bella FS (1979) Mini review on the specificity of naloxone as an opiate antagonist. Life Sci 25:1621–1632
Schaz K, Stock G, Simon W, Schlor KH, Unger T, Rockhold R, Ganten D (1980) Enkephalin effects on blood pressure, heart rate and baroreceptor reflex. Hypertension 2:395–407
Smith TW, Hughes J, Kosterlitz HW, Sosa RP (1976) Enkephalins: Isolation, distribution and function. In: Kosterlitz HW (ed) Opiates and endogenous opioid peptides. North Holland, Amsterdam, pp 57–62
Smyth HS, Sleight P, Pickering GW (1969) Reflex regulation of arterial pressure during sleep in man. A quantitative method of assessing baroreflex sensitivity. Circ Res 24:109–121
Uhl GR, Goodman RR, Kuhar MJ, Childers SR, Snyder SH (1979) Immunohistochemical mapping of enkephalin containing cell bodies, fibres, and nerve terminals in the brain stem of the rat. Brain Res 167:77–91
Wüster M, Schulz R, Herz A (1980) The direction of opioid agonists towards μ, δ and ε receptors in the vas deferens of the mouse and the rat. Life Sci 27:163–170
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Petty, M.A., Reid, J.L. The effect of opiates on arterial baroreceptor reflex function in the rabbit. Naunyn-Schmiedeberg's Arch. Pharmacol. 319, 206–211 (1982). https://doi.org/10.1007/BF00495866
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DOI: https://doi.org/10.1007/BF00495866