Effects of serotonin on cerebral circulation after middle cerebral artery occlusion

View More View Less
  • 1 Division of Neurosurgery, University of Iowa College of Medicine, Iowa City, Iowa
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

✓ Serotonin (5-HT) produces constriction of peripheral collateral blood vessels. Using an animal model, the authors tested the hypothesis that 5-HT constricts collateral vessels in the cerebrum. A branch of the middle cerebral artery (MCA) was occluded proximally and cannulated distally in anesthetized dogs. Blood flow to the area at risk for infarction was detected by perfusing the cannulated MCA branch with microsphere-free blood during systemic injection of radioactive microspheres (shadow flow technique). Blood flow to collateral-dependent and normal cerebrum was measured during intravenous infusion of 5-HT (10 and 40 mg/kg/minute). Serotonin produced a dose-related reduction of blood flow to collateral-dependent cerebrum, increased collateral vessel resistance in large cerebral arteries and collateral vessels, and decreased cerebral artery perfusion pressure. In contrast, blood flow to normal cerebrum was not altered because a decrease in small vessel resistance effectively compensated for a decrease in MCA perfusion pressure. These findings indicate that 5-HT produces constriction of collateral vessels in the cerebrum. This response is clearly different from normal small cerebral vessels, which dilate during 5-HT infusion.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address reprint requests to: Christopher M. Loftus, M.D., Department of Neurosurgery, University of Iowa College of Medicine, Iowa City, Iowa 52242.
  • 1.

    Auer LM, , Leber K, & Sayama I: Effect of serotonin and its antagonist ketanserin on pial vessels. J Cereb Blood Flow Metab 5:517522, 1985 Auer LM, Leber K, Sayama I: Effect of serotonin and its antagonist ketanserin on pial vessels. J Cereb Blood Flow Metab 5:517–522, 1985

    • Search Google Scholar
    • Export Citation
  • 2.

    Baumbach GL, & Heistad DD: Effects of sympathetic stimulation and changes in arterial pressure on segmental resistance of cerebral vessels in rabbits and cats. Circ Res 52:527533, 1983 Baumbach GL, Heistad DD: Effects of sympathetic stimulation and changes in arterial pressure on segmental resistance of cerebral vessels in rabbits and cats. Circ Res 52:527–533, 1983

    • Search Google Scholar
    • Export Citation
  • 3.

    Bonvento G, , Lacombe P, & MacKenzie ET, et al: Evidence for differing origins of the serotonergic innervation of major cerebral arteries and small pial arteries in the rat. J Neurochem 56:681689, 1991 Bonvento G, Lacombe P, MacKenzie ET, et al: Evidence for differing origins of the serotonergic innervation of major cerebral arteries and small pial arteries in the rat. J Neurochem 56:681–689, 1991

    • Search Google Scholar
    • Export Citation
  • 4.

    Buckberg GD, , Luck JC, & Payne DB, et al: Some sources of error in measuring regional blood flow with radioactive microspheres. J Appl Physiol 31:598604, 1971 Buckberg GD, Luck JC, Payne DB, et al: Some sources of error in measuring regional blood flow with radioactive microspheres. J Appl Physiol 31:598–604, 1971

    • Search Google Scholar
    • Export Citation
  • 5.

    Busija DW, , Heistad DD, & Marcus ML: Continuous measurement of cerebral blood flow in anesthetized cats and dogs. Am J Physiol 241:H228H234, 1981 Busija DW, Heistad DD, Marcus ML: Continuous measurement of cerebral blood flow in anesthetized cats and dogs. Am J Physiol 241:H228–H234, 1981

    • Search Google Scholar
    • Export Citation
  • 6.

    Chang JY, & Owman C: Involvement of specific receptors and calcium mechanisms in serotonergic contractile response of isolated cerebral and peripheral arteries from rats. J Pharmacol Exp Ther 242:629636, 1987 Chang JY, Owman C: Involvement of specific receptors and calcium mechanisms in serotonergic contractile response of isolated cerebral and peripheral arteries from rats. J Pharmacol Exp Ther 242:629–636, 1987

    • Search Google Scholar
    • Export Citation
  • 7.

    Chaouloff F: Regulation of 5-HT receptors by corticosteroids: where do we stand? Fund Clin Pharmacol 9:219233, 1995 Chaouloff F: Regulation of 5-HT receptors by corticosteroids: where do we stand? Fund Clin Pharmacol 9:219–233, 1995

    • Search Google Scholar
    • Export Citation
  • 8.

    Cohen RA, , Shepherd JT, & Vanhoutte PM: 5-Hydroxytryptamine can mediate endothelium-dependant relaxation of coronary arteries. Am J Physiol 245:H1077H1080, 1983 Cohen RA, Shepherd JT, Vanhoutte PM: 5-Hydroxytryptamine can mediate endothelium-dependant relaxation of coronary arteries. Am J Physiol 245:H1077–H1080, 1983

    • Search Google Scholar
    • Export Citation
  • 9.

    Coyle P, & Heistad DD: Blood flow through cerebral collateral vessels in hypertensive and normotensive rats. Hypertension 8 (Suppl):II67II71, 1986 Coyle P, Heistad DD: Blood flow through cerebral collateral vessels in hypertensive and normotensive rats. Hypertension 8 (Suppl):II67–II71, 1986

    • Search Google Scholar
    • Export Citation
  • 10.

    Coyle P, & Heistad DD: Blood flow through cerebral collateral vessels one month after middle cerebral artery occlusion. Stroke 18:407411, 1987 Coyle P, Heistad DD: Blood flow through cerebral collateral vessels one month after middle cerebral artery occlusion. Stroke 18:407–411, 1987

    • Search Google Scholar
    • Export Citation
  • 11.

    De Clerck F, , Loots W, & Jageneau A, et al: Correction by ketanserin of the platelet-mediated inhibition of peripheral collateral circulation in the cat: measurement of blood flow with radioactive microspheres. Drug Dev Res 8:149158, 1986 De Clerck F, Loots W, Jageneau A, et al: Correction by ketanserin of the platelet-mediated inhibition of peripheral collateral circulation in the cat: measurement of blood flow with radioactive microspheres. Drug Dev Res 8:149–158, 1986

    • Search Google Scholar
    • Export Citation
  • 12.

    Edvinssson L, , Birath E, & Uddman R, et al: Indoleaminergic mechanisms in brain vessels; localization, concentration, uptake, and in vitro responses of 5-hydroxytryptamine. Acta Physiol Scand 121:291299, 1984 Edvinssson L, Birath E, Uddman R, et al: Indoleaminergic mechanisms in brain vessels; localization, concentration, uptake, and in vitro responses of 5-hydroxytryptamine. Acta Physiol Scand 121:291–299, 1984

    • Search Google Scholar
    • Export Citation
  • 13.

    Faraci F, & Heistad DD: Regulation of large cerebral arteries and cerebral microvascular pressure. Circ Res 66:817, 1990 Faraci F, Heistad DD: Regulation of large cerebral arteries and cerebral microvascular pressure. Circ Res 66:8–17, 1990

    • Search Google Scholar
    • Export Citation
  • 14.

    Faraci FM, & Heistad DD: Endothelium-derived relaxing factor inhibits constrictor responses of large cerebral arteries to serotonin. J Cereb Blood Flow Metab 12:500506, 1992 Faraci FM, Heistad DD: Endothelium-derived relaxing factor inhibits constrictor responses of large cerebral arteries to serotonin. J Cereb Blood Flow Metab 12:500–506, 1992

    • Search Google Scholar
    • Export Citation
  • 15.

    Greene GM, , Muhonen MG, & Detweiler KN, et al: Stem pressure at the origin of intracranial collateral vessels. Am J Physiol 262:H1294H1297, 1992 Greene GM, Muhonen MG, Detweiler KN, et al: Stem pressure at the origin of intracranial collateral vessels. Am J Physiol 262:H1294–H1297, 1992

    • Search Google Scholar
    • Export Citation
  • 16.

    Hamel E, , Fan E, & Linville D, et al: Expression of mRNA for the serotonin 5-hydroxytryptamine1Dβ receptor subtype in human and bovine cerebral arteries. Mol Pharmacol 44:242246, 1993 Hamel E, Fan E, Linville D, et al: Expression of mRNA for the serotonin 5-hydroxytryptamine1Dβ receptor subtype in human and bovine cerebral arteries. Mol Pharmacol 44:242–246, 1993

    • Search Google Scholar
    • Export Citation
  • 17.

    Harper AM, & MacKenzie ET: Cerebral circulatory and metabolic effects of 5-hydroxytryptamine in anaesthetized baboons. J Physiol (Lond) 271:721733, 1977 Harper AM, MacKenzie ET: Cerebral circulatory and metabolic effects of 5-hydroxytryptamine in anaesthetized baboons. J Physiol (Lond) 271:721–733, 1977

    • Search Google Scholar
    • Export Citation
  • 18.

    Heistad DD, , Armstrong MD, & Marcus ML, et al: Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys. Circ Res 54:711718, 1984 Heistad DD, Armstrong MD, Marcus ML, et al: Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys. Circ Res 54:711–718, 1984

    • Search Google Scholar
    • Export Citation
  • 19.

    Heistad DD, , Breese K, & Armstrong ML: Cerebral vasoconstrictor responses to serotonin after dietary treatment of atherosclerosis: implications for transient ischemic attacks. Stroke 18:10681073, 1987 Heistad DD, Breese K, Armstrong ML: Cerebral vasoconstrictor responses to serotonin after dietary treatment of atherosclerosis: implications for transient ischemic attacks. Stroke 18:1068–1073, 1987

    • Search Google Scholar
    • Export Citation
  • 20.

    Heistad DD, , Marcus ML, & Sandberg S, et al: Effect of sympathetic nerve stimulation on cerebral blood flow and on large cerebral arteries of dogs. Circ Res 41:342350, 1977 Heistad DD, Marcus ML, Sandberg S, et al: Effect of sympathetic nerve stimulation on cerebral blood flow and on large cerebral arteries of dogs. Circ Res 41:342–350, 1977

    • Search Google Scholar
    • Export Citation
  • 21.

    Heymann MA, , Payne BD, & Hoffman JI, et al: Blood flow measurements with radionuclide-labeled particles. Prog Cardiovasc Dis 20:5579, 1977 Heymann MA, Payne BD, Hoffman JI, et al: Blood flow measurements with radionuclide-labeled particles. Prog Cardiovasc Dis 20:55–79, 1977

    • Search Google Scholar
    • Export Citation
  • 22.

    Hirzel HO, , Nelson GR, & Sonnenblick EH, et al: Redistribution of collateral blood flow from necrotic to surviving myocardium following coronary occlusion in the dog. Circ Res 39:214222, 1976 Hirzel HO, Nelson GR, Sonnenblick EH, et al: Redistribution of collateral blood flow from necrotic to surviving myocardium following coronary occlusion in the dog. Circ Res 39:214–222, 1976

    • Search Google Scholar
    • Export Citation
  • 23.

    Hirzel HO, , Sonnenblick EH, & Kirk ES: Absence of a lateral border zone of intermediate creatine phosphokinase depletion surrounding a central infarct 24 hours after acute coronary occlusion in the dog. Circ Res 41:673683, 1977 Hirzel HO, Sonnenblick EH, Kirk ES: Absence of a lateral border zone of intermediate creatine phosphokinase depletion surrounding a central infarct 24 hours after acute coronary occlusion in the dog. Circ Res 41:673–683, 1977

    • Search Google Scholar
    • Export Citation
  • 24.

    Hollenberg NK: Segmental vascular responses to serotonin, in Vanhoutte PM (ed): Serotonin and the Cardiovascular System. New York: Raven Press, 1985, pp 165170 Hollenberg NK: Segmental vascular responses to serotonin, in Vanhoutte PM (ed): Serotonin and the Cardiovascular System. New York: Raven Press, 1985, pp 165–170

    • Search Google Scholar
    • Export Citation
  • 25.

    Hollenberg NK: Serotonin, atherosclerosis, and collateral vessel spasm. Am J Hypertens 1:312S316S, 1988 Hollenberg NK: Serotonin, atherosclerosis, and collateral vessel spasm. Am J Hypertens 1:312S–316S, 1988

    • Search Google Scholar
    • Export Citation
  • 26.

    Kamijyo Y, & Garcia JH: Carotid arterial supply of the feline brain. Applications to the study of regional cerebral ischemia. Stroke 6:361369, 1975 Kamijyo Y, Garcia JH: Carotid arterial supply of the feline brain. Applications to the study of regional cerebral ischemia. Stroke 6:361–369, 1975

    • Search Google Scholar
    • Export Citation
  • 27.

    Loftus CM, , Greene GM, & Detwiler KM, et al: Studies of collateral perfusion to canine middle cerebral artery territory. Am J Physiol 259:H560H566, 1990 Loftus CM, Greene GM, Detwiler KM, et al: Studies of collateral perfusion to canine middle cerebral artery territory. Am J Physiol 259:H560–H566, 1990

    • Search Google Scholar
    • Export Citation
  • 28.

    Loftus CM, , Silvidi JA, & Bernstein DD, et al: Effects of preexisting bypass on rCBF and SSEP's following acute stroke in dogs. J Neurosurg 67:421427, 1987 Loftus CM, Silvidi JA, Bernstein DD, et al: Effects of preexisting bypass on rCBF and SSEP's following acute stroke in dogs. J Neurosurg 67:421–427, 1987

    • Search Google Scholar
    • Export Citation
  • 29.

    Lopez JAG, , Armstrong ML, & Harrison DG, et al: Responsiveness of iliac collateral vessels to constrictor stimuli in atherosclerotic primates. Circ Res 63:10201028, 1988 Lopez JAG, Armstrong ML, Harrison DG, et al: Responsiveness of iliac collateral vessels to constrictor stimuli in atherosclerotic primates. Circ Res 63:1020–1028, 1988

    • Search Google Scholar
    • Export Citation
  • 30.

    Lucas JJ, & Hen R: New players in the 5-HT receptor field: genes and knockouts. Trends Pharmacol Sci 16:246252, 1995 Lucas JJ, Hen R: New players in the 5-HT receptor field: genes and knockouts. Trends Pharmacol Sci 16:246–252, 1995

    • Search Google Scholar
    • Export Citation
  • 31.

    Marcus ML, , Heistad DD, & Ehrhardt JC, et al: Total and regional cerebral blood flow measurement with 7-, 10-, 15-, 25-, and 50-µm microspheres. J Appl Physiol 40:501507, 1976 Marcus ML, Heistad DD, Ehrhardt JC, et al: Total and regional cerebral blood flow measurement with 7-, 10-, 15-, 25-, and 50-µm microspheres. J Appl Physiol 40:501–507, 1976

    • Search Google Scholar
    • Export Citation
  • 32.

    Muhonen MG, , Greene GM, & Heistad DD, et al: Mechanisms of redistribution of cerebral blood flow during hypercarbia and seizures. Am J Physiol 266:H2074H2081, 1994 Muhonen MG, Greene GM, Heistad DD, et al: Mechanisms of redistribution of cerebral blood flow during hypercarbia and seizures. Am J Physiol 266:H2074–H2081, 1994

    • Search Google Scholar
    • Export Citation
  • 33.

    Muhonen MG, , Heistad DD, & Faraci FM, et al: Augmentation of blood flow through cerebral collaterals by inhibition of nitric oxide synthase. J Cereb Blood Flow Metab 14:704714, 1994 Muhonen MG, Heistad DD, Faraci FM, et al: Augmentation of blood flow through cerebral collaterals by inhibition of nitric oxide synthase. J Cereb Blood Flow Metab 14:704–714, 1994

    • Search Google Scholar
    • Export Citation
  • 34.

    Muhonen MG, , Loftus CM, & Heistad DD: Effects of adenosine and 2-chloroadenosine on cerebral collateral vessels. J Cereb Blood Flow Metab 15:10751081, 1995 Muhonen MG, Loftus CM, Heistad DD: Effects of adenosine and 2-chloroadenosine on cerebral collateral vessels. J Cereb Blood Flow Metab 15:1075–1081, 1995

    • Search Google Scholar
    • Export Citation
  • 35.

    Muhonen MG, , Sawin PD, & Loftus CM, et al: Pressure-flow relations in canine collateral-dependent cerebrum. Stroke 23:988994, 1992 Muhonen MG, Sawin PD, Loftus CM, et al: Pressure-flow relations in canine collateral-dependent cerebrum. Stroke 23:988–994, 1992

    • Search Google Scholar
    • Export Citation
  • 36.

    Orlandi C, , Blackshear JL, & Hollenberg NK: Specific increase in sensitivity to serotonin of the canine hindlimb collateral arterial tree via the 5-hydroxytryptamine-2 receptor. Microvasc Res 32:121130, 1986 Orlandi C, Blackshear JL, Hollenberg NK: Specific increase in sensitivity to serotonin of the canine hindlimb collateral arterial tree via the 5-hydroxytryptamine-2 receptor. Microvasc Res 32:121–130, 1986

    • Search Google Scholar
    • Export Citation
  • 37.

    Rapport MM: Serum vasoconstrictor (serotonin). V: The presence of creatinine in the complex. A proposed structure of the vasoconstrictor principle. J Biol Chem 180:961965, 1949 Rapport MM: Serum vasoconstrictor (serotonin). V: The presence of creatinine in the complex. A proposed structure of the vasoconstrictor principle. J Biol Chem 180:961–965, 1949

    • Search Google Scholar
    • Export Citation
  • 38.

    Schaub RG, , Meyers KM, & Sande RD: Serotonin as a factor in depression of collateral blood flow following experimental arterial thrombosis. J Lab Clin Med 90:645653, 1977 Schaub RG, Meyers KM, Sande RD: Serotonin as a factor in depression of collateral blood flow following experimental arterial thrombosis. J Lab Clin Med 90:645–653, 1977

    • Search Google Scholar
    • Export Citation
  • 39.

    Sjaastad O: The significance of blood serotonin levels in migraine. A critical review. Acta Neurol Scand 51:200210, 1975 Sjaastad O: The significance of blood serotonin levels in migraine. A critical review. Acta Neurol Scand 51:200–210, 1975

    • Search Google Scholar
    • Export Citation
  • 40.

    Thompson JA, , Wei EP, & Kontos HA: Inhibition by ketanserin of serotonin induced cerebral arteriolar constriction. Stroke 15:10211024, 1984 Thompson JA, Wei EP, Kontos HA: Inhibition by ketanserin of serotonin induced cerebral arteriolar constriction. Stroke 15:1021–1024, 1984

    • Search Google Scholar
    • Export Citation
  • 41.

    Twarog BM, & Page IH: Serotonin content of some mammalian tissues and urine and a method for its determination. Am J Physiol 175:157161, 1953 Twarog BM, Page IH: Serotonin content of some mammalian tissues and urine and a method for its determination. Am J Physiol 175:157–161, 1953

    • Search Google Scholar
    • Export Citation
  • 42.

    Van Nueten JM, , Janssen WJ, & Vanhoutte PM: Serotonin and vascular reactivity. Pharmacol Res Commun 17:585608, 1985 Van Nueten JM, Janssen WJ, Vanhoutte PM: Serotonin and vascular reactivity. Pharmacol Res Commun 17:585–608, 1985

    • Search Google Scholar
    • Export Citation
  • 43.

    Van Nueten JM, , Janssens PAJ, & van Beek J, et al: Vascular efects of ketanserin (R 41 468) a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther 218:217230, 1981 Van Nueten JM, Janssens PAJ, van Beek J, et al: Vascular efects of ketanserin (R 41 468) a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther 218:217–230, 1981

    • Search Google Scholar
    • Export Citation
  • 44.

    Van Riper DA, & Bevan JA: Evidence that neuropeptide Y and norepinephrine mediate electrical field-stimulated vasoconstriction of rabbit middle cerebral artery. Circ Res 68:568577, 1991 Van Riper DA, Bevan JA: Evidence that neuropeptide Y and norepinephrine mediate electrical field-stimulated vasoconstriction of rabbit middle cerebral artery. Circ Res 68:568–577, 1991

    • Search Google Scholar
    • Export Citation
  • 45.

    Verheyen A, , Lauwers F, & Vlaminckx E, et al: Oversensitivity to serotonin of the collateralized vascular bed in rat hindquarters: mechanisms of increased vasoconstriction. Eur J Pharmacol 94:209216, 1991 Verheyen A, Lauwers F, Vlaminckx E, et al: Oversensitivity to serotonin of the collateralized vascular bed in rat hindquarters: mechanisms of increased vasoconstriction. Eur J Pharmacol 94:209–216, 1991

    • Search Google Scholar
    • Export Citation
  • 46.

    Verheyen A, , Vlaminckx E, & Lauwers F, et al: Serotonin-induced blood flow changes in rat hindlegs after unilateral ligation of the femoral artery. Inhibition by the S2 receptor antagonist ketanserin. Arch Int Pharmacol Ther 270:280298, 1984 Verheyen A, Vlaminckx E, Lauwers F, et al: Serotonin-induced blood flow changes in rat hindlegs after unilateral ligation of the femoral artery. Inhibition by the S2 receptor antagonist ketanserin. Arch Int Pharmacol Ther 270:280–298, 1984

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 535 127 8
Full Text Views 115 2 0
PDF Downloads 90 0 0
EPUB Downloads 0 0 0