Summary
The response of the brain vessels to i.a. infused epinephrine, norepinephrine and isoprenaline was evaluated. The experiments were performed on isolated canine brains which were perfused from donor dogs. Total venous outflow and perfusion pressure in the circle of Willis were monitored continuously and total cerebral vascular resistance (CVR) was calculated. Dose response curves were obtained for these three amines, ranging from 0.001–10 μg:
-
1.
Both epinephrine and norepinephrine led to an equal dose dependent increase of CVR ranging from +2% to +61%.
-
2.
Isoprenaline showed a dose dependent decrease of CVR ranging from −5% to −51%.
The effects of the amines on CVR are influenced by their effects on extracerebral vessels and by the cerebral autoregulation. After elimination of the calculated autoregulatory influence the true catecholamine effects on CVR are about 50% of the original effects.
A comparison of equimolar doses (1 nmol) of the three amines after infusion of α-and β-blocking agents showed:
-
1.
The effect of epinephrine and norepinephrine on CVR could be reversed by phentolamine. The dilator potency was as follows: Isoprenaline: Epinephrine : Norepinephrine=1:0.5:0.3.
-
2.
The effect of isoprenaline could be prevented, those of epinephrine were increased by propranolol: The constrictor potency was as follows: Epinephrine : Norepinephrine: Isoprenaline=1:0.5:0.
These results are discussed in relation to the possible influence of non-cerebral tissues including neurocranium and meninges. It is felt that these sources of contamination cannot account for the vasomotor responses and that, consequently, both α-and β-adrenergic activity of the cerebral vessels of the dog has been demonstrated.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ahlquist, R. P.: A study of the adrenotropic receptors. Amer. J. Physiol.153, 586–600 (1948).
Ahlquist, R. P.: The adrenergic receptor. J. Pharm. Sci.55, 359–367 (1966).
Bienmüller, H., Betz, E.: Die Regulation der lokalen corticalen Gehirndurch-durchblutung bei Injektion von Noradrenalin, Pentobarbital und Adrenolitica. Ärztl. Forsch.24, 97–111 (1970)
D'Alecy, L. C., Feigl, E. O.: Sympathetic cerebral vasoconstriction. Fed. Proc.29, 520 (1970).
Falck, B., Nielsen, K. C., Owman, Ch.: Adrenergic innervation of the pial circulation. Scand. J. Lab. clin. Invest. Suppl.102, VI: B96–98 (1968).
Forbes, H. S., Finley, K. H., Nason, G. J.: XXIV A. Action of epinephrine on pia vessels, B. Action of pituitary and pitressin on pial vessels. C. Vasomotor responses in the pia and in the skin. Arch. Neurol. Psychiat. (Chic.)30, 957–979 (1933).
Furchgott, R. F.: Pharmacological characteristics of adrenergic receptors. Fed. Proc.29, 1352–1361 (1970).
Gorshkova, V. K., Saratikov, A. S., Usov, L. A.: Effect of adrenergic drugs on venous drainage from the rat brain. Bull. exp. Biol. Med.72, 779–781 (1971).
Gottstein, U.: Der Hirnkreislauf unter dem Einfluß vasoaktiver Substanzen. Heidelberg: Hüthig 1962.
Green, H. D., Denison, A. B., Jr.: Absence of vasomotor responses to epinephrine and arterenol in an isolated intracranial circulation. Circulat. Res.4, 565–573 (1956).
Greenfield, J. C., Jr., Tindall, G. T.: Effect of Norepinephrine, Epinephrine and Angiotensin on blood flow in the internal carotid artery of man. J. clin. Invest.47, 1672–1684 (1968).
Haevy, M. D.: The effect of different dosages of Adrenaline and Noradrenaline on cerebral and extracranial vessels. Fiziol. Zh. (Mosk.)57, 1677–1684 (1971).
Häggendal, E.: Effects of some vasoactive drugs on the vessels of cerebral grey matter in the dog. Acta physiol. scand.66, Suppl. 258, 55–79 (1965).
Häggendal, E., Nilsson, N. J., Norbäck, B.: On the components of Kr85 clearance curves from the brain of the dog. Acta physiol. scand.66, Suppl. 258, 5–25 (1965).
Häggendal, E., Nilsson, N. J., Norbäck, N.: Effect of blood corpuscle concentration on cerebral blood flow. Acta chir. scand., Suppl.364, 3–12 (1966).
Harper, A. M., Gabrielyan, E. S.: Study of the action of Noradrenaline on the blood flow in the brain using Krypton85. Bull. exp. Biol. Med.69, 536–538 (1970).
Ingvar, D. H., Lassen, N. A.: Regional blood flow of the cerebral cortex determined by Krypton85. Acta physiol. scand.54, 325–338 (1962).
James, I. M., Millar, R. A., Purves, M. J.: Observations on the extrinsic neural control of cerebral blood flow in the baboon. Circulat. Res.25, 77–93 (1969).
James, I. M., Xanalatos, C., Nashat, S.: The effect of changes in CO2 tension and blood pressure on the response of cerebral metabolism and blood flow to an Isoprenaline (isoproterenol) infusion in the dog. Proceedings of CBF-Symposium, London 1970.
Jewell, P. A.: The anastomoses between internal and external carotic circulations in the dog. J. Anat. (Lond.)86, 83–94 (1952).
Lassen, N. A., Høedt-Rasmussen, K., Sørensen, S. C., Skinhøj, E., Cronquist, S., Bödforss, B., Eng, E., Ingvar, D. H.: Regional cerebral blood flow in man determined by krypton85. Neurology (Minneap.)13, 719–727 (1963).
Laubie, M., Drouillat, M.: Action de l'isoproterénol sur l'hémodynamique et le métabolisme cérébral du chien. Arch. int. Pharmacodyn170, 93–98 (1967).
Lluch, S., Katz, L. N.: Effects of Epinephrine and Norepinephrine on the cerebral blood flow of the unanesthetized goat. Fed. Proc.30, 274 (1971).
Lowe, R. F., Gilboe, D. D.: Demonstration of alpha and beta adrenergic receptors in canine cerebral vasculature. Stroke2, 193–200 (1971).
Ludwigs, N., Schneider, M.: Über den Einfluß des Halssympathicus auf die Gehirndurchblutung. Pflügers Arch. ges. Physiol.259, 43–55 (1954).
McClure, C., Jr., Green, H. D.: Cerebral venous outflow in the dog; influence of adrenergic and cholinergic substances. Amer. J. Physiol.197, 1183–1190 (1959).
Meyer, J. S., Lavy, S. S., Ishikawa, S., Symon, L.: Effects of drugs and brain metabolism on internal carotid arterial flow. Amer. J. med. Electronics3, 169–180 (1964).
Olesen, J.: The effect of intracarotic infusion of Adrenaline, Noradrenaline and Angiotensin on the regional cerebral blood flow in man. Proceedings of CBF Symposium, London 1970.
Pratesi, F., Corsi, C., Tesi, M., Spinelli, P., Brunetti, S., Caramelli, L.: Vasoaktive Medikamente mit Wirkung auf den zerebralen Kreislauf. Münch. med. Wschr.110, 1509–1512 (1968).
Raper, A. J., Kontos, H. A., Patterson, J. L., Jr.: Absence of alpha and beta adrenergic responses in the cerebral (pial) arteries and arterioles. Fed. Proc.29, 519 (1970).
Reimann, Ch., Hirsch, L. J.: Total cerebral blood flow measured with electromagnetic flowmeter in unanesthetized goats. Fed. Proc.30, 263 (1971).
Samorajski, T., Marks, B. H.: Localization of tritiated Norepinephrine in mouse brain. J. Histochem. Cytochem.10, 392–399 (1962).
Sokoloff, L.: The actions of drugs on the cerebral circulation. Pharmacol. Rev.11, 1–85 (1959).
Stemmer, E. A., Carey, J. P., Heber, R. E., Connolly, J. E.: The effect of vasoactive drugs on cerebral and peripheral blood flow. J. Amer. med. Ass.200, 538 (1967).
Torre, E. de la, Netsky, M. G., Meshan, J.: Intracranial and extracranial circulations in the dog: Anatomic and angiographic studies. Amer. J. Anat.105, 343 (1959).
Wahl, M., Kuschinsky, W., Bosse, O., Olesen, J., Lassen, N. A., Ingvar, D. H., Thurau, K.: The effect of perivascular microinjection of noradrenaline and adrenaline on the diameter of pia arteries and arterioles. Proceedings from 25th international Congress of Physiological Sciences, Satelite Symposium “Vascular Smooth Muscle”, Tübingen 1971.
Weil-Malherbe, H., Axelrod, H., Tomchick, R.: Blood-brain barrier for adrenaline. Science129, 1226–1227 (1958).
Wiggers, C. J.: The innervation of the cerebral vessels as indicated by the action of drugs. Amer. J. Physiol.20, 206–233 (1907).
Yordanov, B., Vlahov, V.: Effects of α-and β-adrenolytics on cerebral blood supply. Proceedings of CBF Symposium, London 1970.
Zimmer, R., Lang, R., Oberdörster, G.: Post-ischemic reactive hyperemia of the isolated perfused brain of the dog. Pflügers Arch.328, 332–343 (1971).
Zimmer, R., Oberdörster, G., Lang, R.: Druck-Durchblutungskorrelation am isolierten Hirnkresilauf unter Katecholamininfusion. Pflügers Arch., Suppl.335, R22 (1972).
Author information
Authors and Affiliations
Additional information
Supported by the Deutsche Forschungsgemeinschaft.
Rights and permissions
About this article
Cite this article
Oberdörster, G., Lang, R. & Zimmer, R. Direct effects of α-and β-sympathomimetic amines on the cerebral circulation of the dog. Pflugers Arch. 340, 145–160 (1973). https://doi.org/10.1007/BF00588173
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00588173