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Examination of the effects of some 5-HT2 receptor antagonists on central sympathetic outflow and blood pressure in anaesthetised cats

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Summary

Thoracic preganglionic sympathetic nerve activity, blood pressure, heart rate and femoral arterial conductance were recorded in anaesthetised, paralysed cats. Cumulative dose response curves were constructed for the 5-HT2 antagonists cinanserin, ritanserin, cyproheptadine, methiothepin, metergoline and ICI 169,369. These antagonists showed differing effects on the above parameters. Methiothepin and cyproheptadine caused hypotension and sympathoinhibition at low and high doses, whilst metergoline and ritanserin caused these effects at high doses, above 1 mg kg−1. Cinanserin and ICI 169,369 did cause large transient changes in heart rate, blood pressure and sympathetic outflow. However, all the antagonists except ICI 169,369 and methiothepin caused an increase in femoral arterial conductance which was not associated with hypotension. It was therefore concluded that using the above antagonists it was difficult to attribute changes in blood pressure and central sympathetic outflow to blockade of 5-HT2 receptors. However, it is suggested that 5-HT2 receptors may be involved in the control of skeletal muscle and/or skin vascular beds.

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References

  • Adair JR, Hamilton BL, Scappaticci KA, Helke CJ, Gillis RA (1977) Cardiovascular responses to electrical stimulation of the medullary raphe area in the cat. Brain Res 128:141–145

    Google Scholar 

  • Antonaccio MJ, Taylor DG (1977) Reduction in blood pressure, sympathetic nerve discharge and central evoked pressor response by methysergide in anaesthetised cats. Eur J Pharmacol 42:331–338

    Google Scholar 

  • Berger A, Ramirez AJ (1988) Hypotensive spinal serotonergic effect are S1 or S2 receptors involved? Hypertension 11 (Suppl 1):182–185

    Google Scholar 

  • Blackburn TP, Thornber CW, Pearche RJ, Cox B (1988) In vitro studies with ICI 169,369 a chemically novel 5-HT antagonist. Eur J Pharmacol 150:247–256

    Google Scholar 

  • Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena PR (1986) Proposals for the clarification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25:563–576

    Google Scholar 

  • Cohen ML, Fuller RW, Kurz KD (1983a) LY 53857, a selective and potent serotonergic (5-HT2) receptor antagonist, does not lower blood pressure in spontaneously hypertensive rats. J Pharmacol Exp Ther 227:327–332

    Google Scholar 

  • Cohen ML, Fuller RW, Kurz KD (1983b) Evidence that blood pressure reduction by serotonin antagonists is related to alpha receptor blockade in spontaneously hypertensive rats. Hypertension 5:676–681

    Google Scholar 

  • Coote JH, Macleod VH (1974) The influence of bulbospinal monoaminergic pathways on sympathetic nerve activity. J Physiol (Lond) 241:453–475

    Google Scholar 

  • Coote JH, Macleod VH, Fleetwood-Walker S, Gilbey MP (1981) The response of individual sympathetic preganglionic neurones to microelectrophoretically applied endogenous monoamines. Brain Res 215:135–145

    Google Scholar 

  • Dashwood MR, Gilbey MP, Ramage AG (1988) Autoradiographic localisation of 5-HTZ binding sites in the intermediolateral column of the cat. Br J Pharmacol 93 :197P

  • DeGroat WC, Ryall RW (1967) An excitatory action of 5-hydroxytryptamine on sympathetic preganglionic neurones. Exp Brain Res 3:299–305

    Google Scholar 

  • Engel G, Hoyer D, Kalkman HO, Wick HM (1984) Identification of 5-HT2-receptors on longitudinal muscle of the guinea pig ileum. J Receptor Res 4:113–126

    Google Scholar 

  • Gilbey MP, Coote JH, Macleod VH, Peterson DF (1981) Inhibition of sympathetic activity by stimulating in the raphe nuclei and the role of 5-hydroxytryptamine in this effect. Brain Res 226:131–142

    Google Scholar 

  • Ginzel KH (1958) The effect of (+)-lysergic acid diethylamide and other drugs on the carotid sinus reflex. Br J Pharmacol 13:250–259

    Google Scholar 

  • Jilek J, Pomykacek J, Dlabac A, Bartosova M, Provita M (1980) Neuroleptics of the 8-methylthio-10-piperazino-10,11-dihydrobenzo(b,f)thiepin series; new compounds and new procedures. Collection Czechoslov, Chem Commun 45:504–516

    Google Scholar 

  • Kalkman HO, Harms YM, Gelderen VM van, Batink HD, Timmermans PBMWM, Zwieten PA van (1983) Hypotensive activity of serotonin antagonists; correlation with α1-adrenoceptor and serotonin receptor blockade. Life Sci 32:1499–1505

    Google Scholar 

  • Leysen JE, Awouters F, Kennis L, Laudron PM, Vandenberk J, Janssen PAJ(1981) Receptor binding profile of R41 468, a novel antagonist at 5-HTZ receptors. Life Sci 28:1015–1022

    Google Scholar 

  • Leysen JE, Gommeren W, Gompel P van, Wynants J, Janssen PFM, Laudron PM (1985) Receptor-binding properties in vitro and in vivo of ritanserin a very potent and long acting serotonin-S2 antagonist. Mol Pharmacol 27:600–611

    Google Scholar 

  • Lowe DA, Matthews EK, Richardson BP (1981) The calcium antagonistic effects of cyproheptadine on contraction, membrane electrical events and calcium influx in the guinea-pig taenia coli. Br J Pharmacol 74:651–663

    Google Scholar 

  • McCall RB (1983) Serotonergic excitation of sympathetic preganglionic neurons: microiontophoretic study. Brain Res 289:121–127

    Google Scholar 

  • McCall RB (1984) Evidence for a serotonergic mediated sympathoexcitatory responses to stimulation of medullary raphe nuclei. Brain Res 311:131–139

    Google Scholar 

  • McCall RB, Humphrey SJ (1982) Involvement of serotonin in the central regulation of blood pressure: Evidence for a facilitating effect on sympathetic nerve activity. J Pharmacol Exp Ther 222:94–102

    Google Scholar 

  • McCall RB, Schuette MR (1984) Evidence for an alpha-1 receptor mediated central sympathoinhibitory action of ketanserin. J Pharmacol Exp Ther 228:704–710

    Google Scholar 

  • McCall RB, Harris LT (1987) Characterization of the central sympathoinhibitory action of ketanserin. J Pharmacol Exp Ther 241:736–740

    Google Scholar 

  • McCall RB, Harris LT (1988) 5-HTZ receptor agonists increase spontaneous sympathetic nerve activity. Eur J Pharmacol 151:113–116

    Google Scholar 

  • Monachon M-A, Burkard WP, Jalfre M, Haefly W (1972) Blockade of central 5-hydroxytryptamine receptors by methiothepin. Naunyn-Schmiedeberg's Arch Pharmacol 274:192–197

    Google Scholar 

  • Morrison SF, Gebber GL (1984) Raphe neurons with sympathetic-related activity: baroreceptor responses and spinal connections. Am J Physiol 246:R338-R348

    Google Scholar 

  • Neumayr RJ, Hare BD, Franz DN (1974) Evidence for bulbospinal control of sympathetic preganglionic neurons by monoaminergic pathways. Life Sci 14:793–806

    Google Scholar 

  • Ramage AG (1984) The effect of propranolol and other antihypertensive drugs on preganglionic sympathetic nerve activity. Neuropharmacology 23:43–48

    Google Scholar 

  • Ramage AG (1985a) The effects of ketanserin, methysergide and LY 53857 on sympathetic nerve activity. Eur J Pharmacol 113:295–303

    Google Scholar 

  • Ramage AG (1985b) Effects of ritanserin and cinanserin on the cardiovascular system of the cat. Br J Pharmacol 86:598P

    Google Scholar 

  • Ramage AG (1986) Evidence for a central sympathoinhibitory action of prazosin and indoramin. Eur J Pharmacol 121:83–89

    Google Scholar 

  • Ramage AG, Fozard JR (1987) 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 138:179–191

    Google Scholar 

  • Ramage AG, Wouters W, Bevan P (1988) Evidence that the novel antihypertensive agent, flesinoxan causes differential sympathoinhibition and also increases vagal tone by a central action. Eur J Pharmacol 151:373–379

    Google Scholar 

  • Rothlin E (1957) Lysergic acid diethylamide and related substances. Ann NY Acad Sci 66:668–676

    Google Scholar 

  • Tadepalli AS, Ho KW, Buckley JP (1979) Enhancement of reflex bradycardia following intracerebroventricular administration of methysergide in cats. Eur J Pharmacol 69:85–93

    Google Scholar 

  • Vanhoutte PM, Ball SG, Berdeaux A, Cohen ML, Hedner T, McCall R, Ramage AG, Reimann IH, Richer C, Saxena PR, Schalekamp MADH, Struyker-Boudier HAJ, Symoens J, Neuten JM van, Zweiten PA van (1986) Mechanism of action of ketanserin in hypertension. Trends Pharmacol Sci 7:58–59

    Google Scholar 

  • Ward DG, Gunn CG (1976) Locus cocruleus complex: differential modulation of depressor mechanisms. Brain Res 107:407–411

    Google Scholar 

  • Yusof APM, Coote JH (1988) Excitatory and inhibitory actions of intrathecally administered 5-hydroxytryptamine on sympathetic nerve activity in the rat. J Auton Nerv Sys 22:229–236

    Google Scholar 

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  1. Academic Department of Pharmacology, Royal Free Hospital Medical School, Rowland Hill Street, Hampstead, NW3 2PF, London, United Kingdom

    Andrew G. Ramage

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Ramage, A.G. Examination of the effects of some 5-HT2 receptor antagonists on central sympathetic outflow and blood pressure in anaesthetised cats. Naunyn-Schmiedeberg's Arch Pharmacol 338, 601–607 (1988). https://doi.org/10.1007/BF00165623

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  • DOI: https://doi.org/10.1007/BF00165623

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