Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 282, Issue 4, pp 389–400 | Cite as

Effects of centrally applied drugs on pressor responses to hypothalamic stimulation

  • A. Philippu
  • R. Demmeler
  • G. Roensberg
Article

Summary

The posterior hypothalamus of anaesthetized cats was superfused through a push-pull cannula with artificial cerebrospinal fluid and electrically stimulated with the non-insulated tip of the cannula. The hypothalamus was superfused with drugs, and their effects on the pressor responses to hypothalamic stimulation were studied.

Superfusion with low concentrations of clonidine (1×10−5 M or 5×10−5 M) enhanced the pressor responses to hypothalamic stimulation, while the rise of blood pressure caused by stimulation of the hypothalamus was reduced during superfusion with high concentrations of clonidine (1×10−3 M or 1×10−2 M). A moderate concentration of clonidine (1×10−4 M) was ineffective.

Superfusion with carbachol or DMPP (1×10−3 M or 1×10−2 M) elicited a dose-dependent enhancement of the pressor responses to hypothalamic stimulation. Hexamethonium (1×10−2 M) did not affect the rise of blood pressure but abolished the enhancing effects of carbachol and DMPP.

In some experiments the nucleus of the solitary tract was superfused with the push-pull cannula and the posterior hypothalamus was stimulated electrically with a monopolar electrode. Superfusion of the nucleus of the solitary tract with tolazoline (1×10−1 M) enhanced the pressor responses to hypothalamic stimulation.

The present results are compatible with the following views: 1. Low concentrations of clonidine enhance the pressor responses to hypothalamic stimulation by activating the alpha-adrenoceptors of the hypothalamic area; high concentrations of clonidine inhibit the pressor responses by reducing the noradrenaline release via a feed-back mechanism and/or by inhibiting the release of acetylcholine from cholinergic nerve endings of the hypothalamus. 2. Nicotine agents enhance the rise of blood pressure caused by hypothalamic stimulation; their effects are mediated by nicotinic receptors. 3. More than one neurotransmitter seems to be involved in the central modulation of the arterial blood pressure.

Key words

Hypothalamic Stimulation Nucleus of the Solitary Tract Cholinergic Agents Push Pull Cannula Drugs Affecting Alpha-Adrenoreceptors Arterial Blood Pressure 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andén, N.-E., Corrodi, H., Fuxe, K., Hökfelt, B., Hökfelt, T., Rydin, C., Svensson, T.: Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci. 9, 513–523 (1970)Google Scholar
  2. Brezenoff, H. E.: Cardiovascular responses to intrahypothalamic injections of carbachol and certain cholinesterase inhibitors. Neuropharmacol. 11, 637–644 (1972)Google Scholar
  3. Brezenoff, H. E., Jenden, D. J.: Modification of arterial blood pressure in rats following microinjection of drugs into the posterior hypothalamus. Int. J. Neuropharmacol. 8, 593–600 (1969)Google Scholar
  4. Doba, N., Reis, D. J.: Acute fulminating neurogenic hypertension produced by brain stem lesions in the rat. Circulat. Res. 32, 584–593 (1973)Google Scholar
  5. Haeusler, G.: Activation of the central pathway of the baroreceptor reflex, a possible mechanism of the hypotensive action of clonidine. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 231–246 (1973)Google Scholar
  6. Hoefke, W., Kobinger, W.: Pharmakologische Wirkungen des 2-(2,6-Dichlorphenylamino)-2-imidazolinchlorids, einer neuen antihypertensiven Substanz. Arzneimittel-Forsch. 16, 1038–1050 (1966)Google Scholar
  7. Humphreys, P. W., Joels, N., McAllen, R. M.: Modification of the reflex responses to stimulation of carotid sinus baroreceptors during and following stimulation of the hypothalamic defense area in the cat. J. Physiol. (Lond.) 216, 461–482 (1971)Google Scholar
  8. Kobinger, W., Walland, A.: Kreislaufuntersuchungen mit 2-(2,6-Dichlorophenylamino)-2-imidazolin-Hydrochlorid. Arzneimitted-Forsch. (Drug Res.) 17, 292–298 (1967)Google Scholar
  9. Kroneberg, G., Oberdorf, A., Hoffmeister, F., Wirth, W.: Zur Pharmakologie von 2-(2,6-Dimethylphenylamino)-4H-5,6-dihydro-1,3-thiazin (Bayer 1470), eines Hemmstoffes adrenergischer und cholinergischer Neurone. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 256, 257–280 (1967)Google Scholar
  10. Merlis, J. K.: The effect of changes in the calcium content of cerebrospinal fluid on spinal reflex activity in the dog. Amer. J. Physiol. 13, 67–72 (1940)Google Scholar
  11. Philippu, A., Heyd, G., Burger, A.: Release of noradrenaline from the hypothalamus in vivo. Europ. J. Pharmacol. 9, 52–58 (1970)Google Scholar
  12. Philippu, A., Przuntek, H., Roensberg, W.: Superfusion of the hypothalamus with gamma-aminobutyric acid: effect on release of noradrenaline and blood pressure. Naunyn-Schmiedeberg's Arch. Pharmacol. 276, 103–118 (1973a)Google Scholar
  13. Philippu, A., Roensberg, W., Przuntek, H.: Effects of adrenergic drugs on pressor responses to hypothalamic stimulation. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 373–386 (1973b)Google Scholar
  14. Reinoso-Suarez, F.: Topographischer Hirnatlas der Katze: Darmstadt, Merck AG (1961)Google Scholar
  15. Schmitt, H., Schmitt, H., Fernard, S.: Evidence for an alpha-sympathomimetic component in the effect of catapresan on vasomotor centers. Europ. J. Pharmacol. 14, 98–100 (1971)Google Scholar
  16. Starke, K., Altmann, K. P.: Inhibition of adrenergic neurotransmission by clonidine: an action on prejunctional alpha-receptors. Neuropharmacol. 12, 339–347 (1973)Google Scholar
  17. Winne, D.: Zur Auswertung von Versuchsergebnissen: die Prüfung, ob Kurven sich an ihrem Verlauf unterscheiden. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 250, 383–396 (1965)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • A. Philippu
    • 1
  • R. Demmeler
    • 1
  • G. Roensberg
    • 1
  1. 1.Institut für Pharmakologie und Toxikologie der Universität WürzburgWürzburgGermany

Personalised recommendations