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Central effects of paraoxon on haemodynamics in the cat

  • J. H. de Neef
  • A. J. Porsius
Article

Summary

Application of paraoxon into the left vertebral artery (8–80 μg) or both the left and right vertebral artery (4–8 μg) of the anaesthetized cat evoked dose-dependent depressor effects, whereas heart rate was not influenced significantly. Also after systemic administration of paraoxon (150–825 μg·kg−1), while peripheral muscarinic receptors were blocked, depressor effects were still observed. Dose-response curves for the depressor response to paraoxon were established. Infusion of low doses of dexetimide via the vertebral artery prevented the hypotensive action of paraoxon. The distribution of this antimuscarinic drug in the brain was investigated. The depressor effect of paraoxon can be attributed to both a decrease in peripheral resistance and cardiac output. Decerebration and midcollicular transection were carried out in order to elucidate the site and mechanism of action. The depressor effect of paraoxon seems to be mediated by a central mechanism of action located within the lower brain stem.

It is concluded that stimulation of muscarinic receptors in the pontomedullary region gives rise to the observed changes in haemodynamic parameters. Muscarinic receptors in the hypothalamus seem to be of minor importance for the hypotensive action of paraoxon.

Key words

Paraoxon Blood pressure Vertebral artery Central muscarinic receptors Cat 

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References

  1. Bhargava KP, Jain IP, Saxena AK, Sinha JN, Tangri KK (1978) Central adrenoceptors and cholinoceptors in cardiovascular control. Br J Pharm 63:7–15Google Scholar
  2. Brezenoff HE (1972) Cardiovascular responses to intrahypothalamic injections of carbachol and certain cholinesterase inhibitors. Neuropharmacology 11:637–644Google Scholar
  3. Brezenoff HE, Rusin J (1974) Brain acetylcholine mediates the hypertensive response to physostigmine in the rat. Eur J Pharmacol 29:262–266Google Scholar
  4. Brown RV (1960) The effects of intracisternal sarin and pyridine-2-aldoxime methyl methanesulphonate in anaesthetized dogs. Br J Pharm 15:170–174Google Scholar
  5. Dage RC (1979) A centrally mediated prolonged hypotension produced by oxotremorine or pilocarpine. Br J Pharm 65:15–21Google Scholar
  6. Dirnhuber P, Cullumbine H (1953) The effect of anticholinesterase agents on rat's blood pressure. Br J Pharm 8:466–475Google Scholar
  7. Guertzenstein PG (1973) Blood pressure effects obtained by drugs applied to the ventral surface of the brain stem. J Physiol 229:395–408Google Scholar
  8. Hamilton FN, Minzel JC, Schlobohm RM (1967) Measurement of cardiac output by two methods in dogs. J Appl Physiol 22:362–364Google Scholar
  9. Heymans C, Pochet A, van Houtte H (1956) Contributions à la pharmacologie du sarin et du tabun. Arch Int Pharmacodyn 104:293–332Google Scholar
  10. Hughes R (1970) Integration and differentiation of phasic aortic flow and continuous recording of peripheral vascular resistance. Br J Pharm 39:232P-233PGoogle Scholar
  11. Janssen PAJ, Niemegeers CJE, Schellekens KHL, Demoen P, Lenaerts FM, van Nueten JM, van Wijngaarden I, Brugmans J (1971) Benzetimide and its optical isomers. Arzneim Forsch 21:1365–1373Google Scholar
  12. Koller EA, Jenny M (1969) A technique for standard decerebration by high-frequency coagulation. Brain Res 14:549–552Google Scholar
  13. Laduron PM, Verwimp M, Leysen JE (1979) Stereo-specific in vitro binding of 3H-dexetimide to brain muscarnic receptors. J Neurochem 32:421Google Scholar
  14. Lang WJ, Rush ML (1973) Cardiovascular responses to injections of cholinomimetic drugs into the cerebral ventricles of anaesthetized dogs. Br J Pharm 47:196–205Google Scholar
  15. Neef JH de, Porsius AJ (1980) The effects of paraoxon on haemodynamics and cholinesterase activity in the cat. Joint Meeting of the Scandinavian and German Pharmacological Societies. Naunyn-Schmiedeberg's Arch Pharmacol (Suppl) 313:R64Google Scholar
  16. Noble MIM, Trenchard D, Guz A (1966) Left ventricular ejection in conscious dogs: 1. Circ Res 19:139–147Google Scholar
  17. Philippu A, Bohuschke A (1976) Hypothalamic superfusion with muscarinic drugs. Naunyn-Schmiedeberg's Arch Pharmacol 292:1–7Google Scholar
  18. Porsius AJ, Mutschler E, van Zwieten PA (1978) The central action of various arecaidine esters (arecoline derivatives) on blood pressure and heart rate in the cat. Arzneium Forsch (Drug Res) 28:1373–1376Google Scholar
  19. Porsius AJ, Fronik GM (1980) Hypotensive effect and kinetic behaviour of isocarecaidine-propyl-ester in the cat. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft. Naunyn-Schmiedeberg's Arch Pharmacol (Suppl) 311:R46Google Scholar
  20. Porsius AJ (1980) The simultaneous infusion of drugs via the left and right vertebral artery of the cat: a modified animal model for the study of possible central actions of drugs upon the lower brain stem. Arch Int Pharmacodyn Thér 248:260–271Google Scholar
  21. Preston E, Heath C (1972) Depression of the vasomotor system in rabbits poisoned with an organophosphate anticholinesterase. Arch Int Pharmacodyn 200:245–254Google Scholar
  22. Stewart WC, Anderson EA (1968) Effect of a cholinesterase inhibitor when injected into the medulla of the rabbit. J Pharmacol Exp Ther 162:309–318Google Scholar
  23. Tangri KK, Jain IP, Bhargava KP (1969) Role of central cholinoceptors in cardiovascular regulation. Progr Brain Res 14:123–130Google Scholar
  24. Varagic V, Krstic M (1966) Adrenergic activation by anticholinesterases. Pharm Rev 18:799–800Google Scholar
  25. Wildt DJ de (1980) Further studies on the central hypotensive action of physostigmine. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft. Naunyn-Schmiedeberg's Arch Pharmacol (Suppl) 311:R46Google Scholar
  26. Zwieten PA van (1975) Antihypertensive drug with a central action. Progr Pharmacol 1:1–63Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • J. H. de Neef
    • 1
  • A. J. Porsius
    • 1
  1. 1.Department of Pharmacy, Division of PharmacotherapyUniversity of AmsterdamAmsterdamThe Netherlands

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