Summary
The effects of microinjection of histamine and its antagonists into mesencephalic nucleus dorsalis raphe, were investigated on mean arterial pressure and heart rate in cats to elucidate the nature and role of histaminergic receptors in cardiovascular regulation. Microinjection of histamine (5 and 10 μg) into nucleus dorsalis raphe elicited both inhibitory and excitatory cardiovascular responses respectively. On the other hand, microinjection of H2-receptor blocker, cimetidine (10 μg) resulted in hypertension and tachycardia while H1-receptor antagonist, mepyramine (10 μg) microinjection evoked hypotension and bradycardia. Furthermore, local pretreatment with cimetidine and mepyramine blocked the inhibitory and excitatory cardiovascular responses of graded doses of histamine microinjection. These H1 and H2 receptors are localized in nucleus dorsalis raphe since microinjection of histamine into adjoining neural structures did not evoke any cardiovascular change. Furthermore, both the inhibitory and excitatory cardiovascular responses to histamine microinjection could not be observed in animals with spinal cord transection and in animals pretreated with p-chlorophenylalanine while they could be observed in bilateral cervical vagotomized animals. Thus, it appears that these cardiovascular responses to microinjection of histamine into nucleus dorsalis raphe, are due to modulation of serotonergic bulbospinal influence on sympathetic preganglionic neurones in the spinal cord. Moreover, the excitatory cardiovascular responses of high dose of histamine (10 μg) seem to result from a local release of noradrenaline since they were blocked by prior microinjection of guanethidine and piperoxan into nucleus dorsalis raphe. A release of noradrenaline in turn, modulates the activity of the neurones of the nucleus by acting on α adrenoceptors and thereby alters the activity of sympathetic preganglionic neurones. These α adrenoceptors appear to be of α1 type (Saxena et al. 1985, 1987) since phenylephrine microinjection evoked excitatory cardiovascular responses could be blocked by piperoxan.
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References
Aghajanian GK, Wang RY (1977) Habenular and other mid brain raphe afferents demonstrated by a modified retrograde tracing technique. Brain Res 122:229–242
Brezenoff HE, Jenden DJ (1969) Modification of arterial blood pressure in rats following microinjections of drugs into the posterior hypothalamus. Int J Neuropharm 8: 593–600
Burkard WP (1978) Histamine H2-receptor binding with (3H)-cimetidine in brain. Eur J Pharmacol 50:449–450
Cabot JB (1979) Raphe inhibition of sympathetic preganglionic neurones. Science 203:184–196
Dalbarre B, Schmitt H, Senon D (1976) Effect of activation of H1 and H2 receptors on central cardiovascular structures in cats and behaviour in chickens. Br J Pharmacol 58: 443P
Finch L, Hicks PE (1976a) The cardiovascular effects of intraventricularly administered histamine in the anaesthetized rats. Naunyn-Schmiedeberg's Arch Pharmacol 293:151–157
Finch L, Hicks PE (1976b) Central hypertensive action of histamine in conscious normotensive rats. Eur J Pharmacol 36:263–266
Finch L, Hicks PE (1977) Involvement of hypothalamic histamine receptors in central cardiovascular actions of histamine. Neuropharmacology 16:211–218
Finch L, Harvey CA, Hicks PE (1978) Clonidine induced hypotension: Further evidence for a central interaction with H2-receptor antagonists in the rat. Neuropharmacology 17:307–313
Fuxe K, Jonsson G (1974) Further mapping of central 5-hydroxytryptamine neurones: Studies with neurotoxic dihydroxytryptamine. In: Costa E, Gessa GL, Sandler M (eds) Serotonin new vistas. Raven Press, New York, pp 1–12
Garberg M, Barbin G, Llorens C, Palacios JM, Pollard H (1980) Recent development in histamine research: Pathways and receptors. In: Essman WB (ed) Transmitters, receptors and drugs action. Spectrum Publications, New York, pp 179–202
Granata AR, Reis DJ (1987) Hypotension and bradycardia elicited by histamine into the Cl area of the rostral ventrolateral medulla. Eur J Pharmacol 136:157–162
Haas HL, Hosli L, Anderson EG, Wolf P (1975) Action of histamine and metabolites on single neurones of the mammalian central nervous system. In: Bossier JR, Hippius P, Pichat P (eds) Neuropsychopharmacology. Excerpta Medica, Amsterdam, pp 589–596
Haas HL, Wolf P (1977) Central actions of histamine microelectrophoretic studies. Brain Res 122:269–279
Karppanen H, Paakari I, Paakari P, Houtari R, Orma AL (1976) Possible involvement of central histamine H2-receptors in the hypotensive effect of clonidine. Nature 259:587–588
Koe BK, Weissman A (1966) p-Chlorophenylalanine: A specific depletor of brain serotonin. J Pharmacol Exp Ther 154:499–516
Mohrland JS, Gebhard GF (1980) Effects of local electrical stimulation and morphine microinjection in the periaqueductal grey of the rat mesencephalon on neural activity in the medullary recticular formation. Brain Res 201:23–37
Neumayr RJ, Hare PD, Franz DL (1974) Evidence for bulbospinal control of sympathetic preganglionic neurones by monoaminergic pathways. Lije Sciences 14:793–806
Palacios JM, Wamsely JK, Kuhar MJ (1981) The distribution of histamine H1-receptors in the rat brain: An autoradiographic study. Neurosciences 6:15–37
Palacios JM, Young WS, Kuhar MJ (1979) Autoradiographic localization of H1-histamine receptors in brain using (3H)-mepyramine: Preliminary studies. Eur J Pharmacol 58:295–304
Philippu A, Bald M, Kraus A, Dietl H (1984) In vivo release by histamine agonists and antagonists of endogenous catecholamines in the cat hypothalamus. Naunyn-Schmiedeberg's Arch Pharmacol 326:116–123
Pollard H, Llorens-Cortes C, Barbin G, Garberg M, Schwartz JC (1978) Histamine and histadine decarboxylase in brain stem nuclei: Distribution and decrease after lesions. Brain Res 157:178–181
Pollard H, Pachot I, Legrain P, Buttin G, Schwartz JC (1985) Development of monoclonal antibody against l-histadine decarboxylase as a selective tool for localization of histamine synthesizing cells. In: Gannellin CR, Schwartz JC (eds) Frontiers in histamine research, Advances in the biosciences, vol 51. Pergamon, London, pp 103–117
Reader TA (1982) Catecholamines and serotonin in rat frontal cortex after p-chlorophenylalanine and 6-hydroxydopamine-absolute amounts and ratios. Brain Res Bull 8:527–534
Sakai K, Touret M, Salvert D, Leger L, Jouvet M (1977) Afferent projections to the cat locus coeruleus as visualized by the horseradish peroxidase technique. Brain Res 119:21–24
Saxena AK, Saksena AK, Agnihotri MS, Vrat S, Tangri KK, Bhargava KP (1985) Cardiovascular responses elicited by microinjection of monoamines into mesencephalic nucleus dorsalis raphe in cats. Naunyn-Schmiedeberg's Arch Pharmacol 329:141–145
Saxena AK, Saksena AK, Vrat S, Tangri KK (1987) Presence of opioid receptors in mesencephalic nucleus dorsalis raphe concerned in cardiovascular regulation in cats. Naunyn-Schmiedeberg's Arch Pharmacol 336:81–86
Schwartz JC, Barbin G, Garberg M, Llorens C, Palacios JM (1978) Histaminergic systems in brain. In: Simon P (ed) Advances in pharmacology and therapeutics, vol 2. Pergamon Press, Oxford, pp 171–180
Schwartz JC, Palacios JM, Barbin G (1979) Histamine receptors in mammalian brain: Characters and modifications studied electrophysiologically and biochemically. In: Yellin TO (ed) Histamine receptors. Spectrum Publications, New York, pp 161–183
Smits JFM, Van Esson H, Struyker-Boudier HAJ (1978) Serotonin mediated cardiovascular responses to electrical stimulation of raphe nuclei in the rat. Life Science 23:173–178
Snider RS, Neimer WT (1961) Stereotaxic atlas of the cat brain. The University of Chicago Press, Chicago, USA
Steinbusch HWM, Mulder AH (1985) Localization and projections of histamine immunoreactive neurones in central nervous system of the rat. In: Gannellin CR, Schwartz JC (eds) Frontiers in histamine research, Advances in biosciences, vol 51. Pergamon, London, pp 119–130
Watanabe T, Taguchi Y, Hayashi H, Wada H, Tanaka J, Shiosaka S (1983) Evidence for the presence of a histaminergic neurone system in rat brain: An immunohistochemical analysis. Neurosci Lett 39:249–254
Watanabe RT, Taguchi Y, Shiosaka S, Tanaka J, Kubota H (1984) Distribution of histaminergic neurones system in central nervous system of rats: A fluorescent immunohistochemical analysis with histadine decarboxylase as a marker. Brain Res 295: 13–25
Weiss KR, Cohen JL, Kupfermann I (1978a) Modulatory control of buccal musculature by a serotonergic neurone (metacerebral cell) in Aplysia. J Neurophysiol 41:181–203
Weiss KR, Shapiro E, Kooster J, Kupfermann I (1978b) A histaminergic synaptic potential produced by a voltage-dependant apparent decrease of conductance in the metacerebral cell of Aplysia. Soc Neurosci Abstr 4:657
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Tangri, K.K., Gupta, G.P. & Vrat, S. Role of histamine receptor in mesencephalic nucleus dorsalis raphe in cardiovascular regulation. Naunyn-Schmiedeberg's Arch Pharmacol 339, 557–563 (1989). https://doi.org/10.1007/BF00167261
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DOI: https://doi.org/10.1007/BF00167261