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. 1989 Jan;96(1):125–132. doi: 10.1111/j.1476-5381.1989.tb11792.x

Carotid haemodynamics in pigs during infusions of 8-OH-DPAT: reduction in arteriovenous shunting is mediated by 5-HT1-like receptors.

A H Bom 1, P D Verdouw 1, P R Saxena 1
PMCID: PMC1854297  PMID: 2522333

Abstract

1. The effects of intracarotid infusions of 8-hydroxy-2-[di-n-propyl-amino]-tetralin (8-OH-DPAT) on heart rate, blood pressure and carotid blood flow and its distribution were studied in anaesthetized pigs by use of radioactive microspheres of 15 microns diameter. 2. Control experiments with physiological saline showed that systemic and carotid haemodynamics remain essentially unchanged during the experimental period. In contrast to results obtained in rat, cat and dog experiments, 8-OH-DPAT did not decrease arterial blood pressure. 3. 8-OH-DPAT, which has a high affinity and is selective for the 5-HT1A recognition site, caused a dose-related decrease in arteriovenous anastomotic (non-nutrient) blood flow, resulting in a decrease in carotid blood flow. At the highest dose used, a small increase in arteriolar (nutrient) blood flow was observed. 4. The decrease in arteriovenous anastomotic and carotid blood flow induced by 8-OH-DPAT was not significantly modified by pretreatment with the 5-HT2 receptor antagonist ketanserin (0.5 mg kg-1), but was markedly reduced by pretreatment with methiothepin (1 mg kg-1), which blocks both the 5-HT1-like and 5-HT2 receptors. 5. It is concluded that the effects of 8-OH-DPAT on arteriovenous anastomotic blood flow are mediated by 5-HT1-like receptors. These receptors, however, cannot yet be classified as belonging to 5-HT1A receptor subtype. Since a number of antimigraine drugs reduce arteriovenous shunting, it is tempting to suggest that 8-OH-DPAT may have similar clinical efficacy.

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Selected References

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  1. Bradley P. B., Engel G., Feniuk W., Fozard J. R., Humphrey P. P., Middlemiss D. N., Mylecharane E. J., Richardson B. P., Saxena P. R. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology. 1986 Jun;25(6):563–576. doi: 10.1016/0028-3908(86)90207-8. [DOI] [PubMed] [Google Scholar]
  2. Di Francesco G. F., Petty M. A., Fozard J. R. Antihypertensive effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in conscious dogs. Eur J Pharmacol. 1988 Mar 1;147(2):287–290. doi: 10.1016/0014-2999(88)90789-3. [DOI] [PubMed] [Google Scholar]
  3. Doenicke A., Brand J., Perrin V. L. Possible benefit of GR43175, a novel 5-HT1-like receptor agonist, for the acute treatment of severe migraine. Lancet. 1988 Jun 11;1(8598):1309–1311. doi: 10.1016/s0140-6736(88)92122-8. [DOI] [PubMed] [Google Scholar]
  4. Doods H. N., Boddeke H. W., Kalkman H. O., Hoyer D., Mathy M. J., van Zwieten P. A. Central 5-HT1A receptors and the mechanism of the central hypotensive effect of (+)8-OH-DPAT, DP-5-CT, R28935, and urapidil. J Cardiovasc Pharmacol. 1988 Apr;11(4):432–437. doi: 10.1097/00005344-198804000-00008. [DOI] [PubMed] [Google Scholar]
  5. Eisele J. H., Smith N. T. Cardiovascular effects of 40 percent nitrous oxide in man. Anesth Analg. 1972 Nov-Dec;51(6):956–963. [PubMed] [Google Scholar]
  6. Fozard J. R., Mir A. K., Middlemiss D. N. Cardiovascular response to 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the rat: site of action and pharmacological analysis. J Cardiovasc Pharmacol. 1987 Mar;9(3):328–347. doi: 10.1097/00005344-198703000-00010. [DOI] [PubMed] [Google Scholar]
  7. Gradin K., Pettersson A., Hedner T., Persson B. Acute administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT-receptor agonist, causes a biphasic blood pressure response and a bradycardia in the normotensive Sprague-Dawley rat and in the spontaneously hypertensive rat. J Neural Transm. 1985;62(3-4):305–319. doi: 10.1007/BF01252244. [DOI] [PubMed] [Google Scholar]
  8. Heuring R. E., Peroutka S. J. Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. J Neurosci. 1987 Mar;7(3):894–903. doi: 10.1523/JNEUROSCI.07-03-00894.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hoyer D., Engel G., Kalkman H. O. Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (-)[125I]iodocyanopindolol, [3H]mesulergine and [3H]ketanserin. Eur J Pharmacol. 1985 Nov 26;118(1-2):13–23. doi: 10.1016/0014-2999(85)90658-2. [DOI] [PubMed] [Google Scholar]
  10. Humphrey P. P., Feniuk W., Perren M. J., Connor H. E., Oxford A. W., Coates L. H., Butina D. GR43175, a selective agonist for the 5-HT1-like receptor in dog isolated saphenous vein. Br J Pharmacol. 1988 Aug;94(4):1123–1132. doi: 10.1111/j.1476-5381.1988.tb11630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Johnston B. M., Saxena P. R. The effect of ergotamine on tissue blood flow and the arteriovenous shunting of radioactive microspheres in the head. Br J Pharmacol. 1978 Jul;63(3):541–549. doi: 10.1111/j.1476-5381.1978.tb07810.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Martin G. E., Lis E. V., Jr Hypotensive action of 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) in spontaneously hypertensive rats. Arch Int Pharmacodyn Ther. 1985 Feb;273(2):251–261. [PubMed] [Google Scholar]
  13. McCall R. B., Patel B. N., Harris L. T. Effects of serotonin1 and serotonin2 receptor agonists and antagonists on blood pressure, heart rate and sympathetic nerve activity. J Pharmacol Exp Ther. 1987 Sep;242(3):1152–1159. [PubMed] [Google Scholar]
  14. Middlemiss D. N., Fozard J. R. 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol. 1983 May 20;90(1):151–153. doi: 10.1016/0014-2999(83)90230-3. [DOI] [PubMed] [Google Scholar]
  15. Pazos A., Palacios J. M. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res. 1985 Nov 4;346(2):205–230. doi: 10.1016/0006-8993(85)90856-x. [DOI] [PubMed] [Google Scholar]
  16. Pedigo N. W., Yamamura H. I., Nelson D. L. Discrimination of multiple [3H]5-hydroxytryptamine binding sites by the neuroleptic spiperone in rat brain. J Neurochem. 1981 Jan;36(1):220–226. doi: 10.1111/j.1471-4159.1981.tb02397.x. [DOI] [PubMed] [Google Scholar]
  17. Peroutka S. J. Pharmacological differentiation and characterization of 5-HT1A, 5-HT1B, and 5-HT1C binding sites in rat frontal cortex. J Neurochem. 1986 Aug;47(2):529–540. doi: 10.1111/j.1471-4159.1986.tb04532.x. [DOI] [PubMed] [Google Scholar]
  18. Peroutka S. J., Snyder S. H. Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol. Mol Pharmacol. 1979 Nov;16(3):687–699. [PubMed] [Google Scholar]
  19. Ramage A. G., Fozard J. R. Evidence that the putative 5-HT1A receptor agonists, 8-OH-DPAT and ipsapirone, have a central hypotensive action that differs from that of clonidine in anaesthetised cats. Eur J Pharmacol. 1987 Jun 19;138(2):179–191. doi: 10.1016/0014-2999(87)90431-6. [DOI] [PubMed] [Google Scholar]
  20. Saxena P. R. Arteriovenous shunting and migraine. Res Clin Stud Headache. 1978;6:89–102. [PubMed] [Google Scholar]
  21. Saxena P. R., Duncker D. J., Bom A. H., Heiligers J., Verdouw P. D. Effects of MDL 72222 and methiothepin on carotid vascular responses to 5-hydroxytryptamine in the pig: evidence for the presence of "5-hydroxytryptamine1-like" receptors. Naunyn Schmiedebergs Arch Pharmacol. 1986 Jul;333(3):198–204. doi: 10.1007/BF00512930. [DOI] [PubMed] [Google Scholar]
  22. Saxena P. R., Schamhardt H. C., Forsyth R. P., Hoeve J. Computer programs for the radioactive microsphere technique. Determination of regional blood flows and other haemodynamic variables in different experimental circumstances. Comput Programs Biomed. 1980 Dec;12(2-3):63–84. doi: 10.1016/0010-468x(80)90053-7. [DOI] [PubMed] [Google Scholar]
  23. Saxena P. R., Verdouw P. D. 5-Carboxamide tryptamine, a compound with high affinity for 5-hydroxytryptamine1 binding sites, dilates arterioles and constricts arteriovenous anastomoses. Br J Pharmacol. 1985 Feb;84(2):533–544. doi: 10.1111/j.1476-5381.1985.tb12938.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Saxena P. R., Verdouw P. D. Effects of methysergide and 5-hydroxytryptamine on carotid blood flow distribution in pigs: further evidence for the presence of atypical 5-HT receptors. Br J Pharmacol. 1984 Aug;82(4):817–826. doi: 10.1111/j.1476-5381.1984.tb16478.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Saxena P. R., Verdouw P. D. Redistribution by 5-hydroxytryptamine of carotid arterial blood at the expense of arteriovenous anastomotic blood flow. J Physiol. 1982 Nov;332:501–520. doi: 10.1113/jphysiol.1982.sp014427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Spierings E. L., Saxena P. R. Antimigraine drugs and cranial arteriovenous shunting in the cat. Neurology. 1980 Jul;30(7 Pt 1):696–701. doi: 10.1212/wnl.30.7.696. [DOI] [PubMed] [Google Scholar]
  27. Spierings E. L., Saxena P. R. Effect of isometheptene on the distribution and shunting of 15 microM microspheres throughout the cephalic circulation of the cat. Headache. 1980 Mar;20(2):103–106. doi: 10.1111/j.1526-4610.1980.hed2002103.x. [DOI] [PubMed] [Google Scholar]
  28. Verdouw P. D., Jennewein H. M., Heiligers J., Duncker D. J., Saxena P. R. Redistribution of carotid artery blood flow by 5-HT: effects of the 5-HT2 receptor antagonists ketanserin and Wal 1307. Eur J Pharmacol. 1984 Jul 20;102(3-4):499–509. doi: 10.1016/0014-2999(84)90571-5. [DOI] [PubMed] [Google Scholar]
  29. Verdouw P. D., Jennewein H. M., Mierau J., Saxena P. R. N-(3-acetylaminophenyl)piperazine hydrochloride (BEA 1654), a putative 5-HT1 agonist, causes constriction of arteriovenous anastomoses and dilatation of arterioles. Eur J Pharmacol. 1985 Jan 8;107(3):337–346. doi: 10.1016/0014-2999(85)90259-6. [DOI] [PubMed] [Google Scholar]

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