Abstract
Serotonin causes constriction of the vascular smooth muscle cells and platelet aggregation mainly through activation of 5-HT2-serotonergic receptors. The vasoconstrictor effects of serotonin can be counteracted by the prejunctional inhibition of adrenergic neurotransmission and predominantly by the release of endothelium derived relaxing factor. These effects of the monoamine are caused by activation of 5-HT1-like serotonergic receptors. Endothelium derived relaxing factor also prevents platelet aggregation and adhesion to the vascular wall. When the endothelium is dysfunctional, as is the case in atherosclerosis or after the endothelium has recovered from an injury, serotonin cannot induce the liberation of endothelium derived relaxing factor but will cause the release of endothelium derived contracting factor. As a result platelet aggregation and vasoconstriction can occur. Serotonin may also increase the viscosity of the blood by an action on red and white blood cells, which may cause a further impairment of blood flow. At the same time platelet derived growth factor, released from aggregating blood platelets may cause proliferation of the vascular smooth muscle cells which participates in the progression of atherosclerosis.
Keywords
- Platelet Aggregation
- Vascular Smooth Muscle Cell
- Adrenergic Nerve
- Endothelium Derive Relaxing Factor
- Porcine Coronary Artery
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alheid, U., Frölich, J. C. and Förstermann, U. (1987) ‘Endothelium-derived relaxing factor from cultured human endothelial cells inhibits aggregation of human platelets’, Thromb. Res. 47, 561–571.
Azuma, H., Ishikawa, M. and Sekizaki, S. (1986) ‘Endothelium-dependent inhibition of platelet aggregation’, Br. J. Pharmacol. 88, 411–415.
Bevan, J. A. and Heptinstall, S. (1983) ‘Effects of ketanserin and mepyramine on platelet aggregation and on the uptake of 5-hydroxytryptamine into platelets’, Thromb. Res. 30, 415–423.
Bogar, L., Matrai, A., Walker, R. T., Flute, P. T. and Dormandy, J. A. (1985) ‘Haemorheological effects of a 5-HT2-receptor antagonist (ketanserin)’, Clin. Haemorheol. 5, 115–121.
Bult, H., Fret, H. R. L., Van den Bossche, R. M. and Herman, A. G. (1988) ‘Platelet inhibition by endothelium-derived relaxing factor from the rabbit perfused aorta’, Br. J. Pharmacol. 95, 1308–1314.
Bush, L. R., Campbell, W. B., Kern, K., Tilton, G. D., Apprill, P., Ashton, J., Schmitz, J., Buja, L. M. and Willerson, J. T. (1984) ‘The effects of alpha2-adrenergic and serotonergic receptor antagonists on cyclic blood flow alterations in stenosed canine coronary arteries’, Circ. Res. 55, 642–652.
Cocks, T. M. and Angus, J. A. (1983) ‘Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin’, Nature (Lond.) 305, 627–630.
Cohen, M. L., Fuller, R. W. and Wiley, K. S. (1981) ‘Evidence for 5-HT2 receptors mediating contraction in vascular smooth muscle’, J. Pharmacol. Exp. Ther. 218, 421–425.
Cohen, R. A. (1985a) ‘Platelet-induced neurogenic coronary contractions due to accumulation of the false neurotransmitter, 5-hydroxytryptamine’, J. Clin. Invest. 75, 286–292.
Cohen, R. A. (1985b) ‘Serotonergic prejunctional inhibition of canine coronary adrenergic nerves’, J. Pharmacol. Exp. Ther. 235, 76–80.
Cohen, R. A. (1987) ‘Inhibition of adrenergic neurotransmission in canine tibial artery after exposure to 5-hydroxytryptamine in vitro’ J. Pharmacol. Exp. Ther. 242, 493–498.
Cohen, R. A., Shepherd, J. T. and Vanhoutte, P. M. (1983a) ‘5-Hydroxytryptamine can mediate endothelium-dependent relaxation of coronary arteries’, Am. J. Physiol. 245, H1077–H1080.
Cohen, R. A., Shepherd, J. T. and Vanhoutte, P. M. (1983b) ‘Inhibitory role of the endothelium in the response of isolated coronary arteries to platelets’, Science 221, 273–274.
Cohen, R. A., Shepherd, J. T. and Vanhoutte, P. M. (1984) ‘Endothelium and asymmetrical responses of the coronary arterial wall’, Am. J. Physiol. 247, H403–H408.
Cohen, R. A., Zitnay, K. M. and Weisbrod, R. M. (1987) ‘Accumulation of 5-hydroxytryptamine leads to dysfunction of adrenergic nerves in canine coronary artery following intimal damage in vivo’, Circ. Res. 61, 829–833.
Collis, M. G. and Vanhoutte, P. M. (1977) ‘Vascular reactivity of isolated perfused kidneys from male and female spontaneously hypertensive rats’, Circ. Res. 41, 759–767.
de Chaffoy de Courcelles, D., Roevens, P., Van Belle, H. and De Clerck, F. (1987) ‘The synergistic effect of serotonin and epinephrine on the human platelet at the level of signal transduction’, FEBS Lett. 219, 283–288.
De Clerck, F., David, J. L. and Janssen, P. A. J. (1982) ‘Inhibition of 5-hydroxytryptamine-induced and amplified human platelet aggregation by ketanserin (R 41 468), a selective 5-HT 2 receptor antagonist’, Agents Actions 12, 388–397.
De Clerck, F. and Herman, A. G. (1983) ‘5-Hydroxytryptamine and platelet aggregation’, Fed. Proc. 42, 228–232.
De Clerck, F. and Van Nueten, J. M. (1982) ‘Platelet-mediated vascular contractions: Inhibition of the serotonergic component by ketanserin’, Thromb. Res. 27, 713–727.
De Clerck, F., Van Nueten, J. M. and Reneman, R. S. (1984) ‘Platelet- vessel wall interactions: implication of 5-hydroxytryptamine. A review’, Agent Actions 15, 612–626.
De Clerck, F. and Xhonneux, B. (1985) ‘Effects of ketanserin, a selective 5-HT2 serotonergic antagonist, in the secondary recruitment of human platelets in vitro’, Agents Actions 17, 515–526.
De Clerck, F., Xhonneux, B. and de Chaffoy de Courcelles, D. (1988) ‘Functional expression of the amplification reaction between serotonin and epinephrine on platelets’, J. Cardiovasc. Pharmacol. 11 (Suppl. 1), S1–S5.
De Clerck, F., Xhonneux, B., Leysen, J. E. and Janssen, P. A. J. (1984) ‘Evidence for functional 5-HT2 receptor sites on human blood platelets’, Biochem. Pharmacol. 33, 2807–2811.
De Clerck, F., Xhonneux, B., Leysen, J. E. and Janssen, P. A. J. (1984) ‘The involvement of 5-HT2-receptor sites in the activation of cat platelets’, Thromb. Res. 33, 305–321.
De Cree, J., Geukens, H., Leempoels, J. and Verhaegen, H. (1985b) ‘The effects of ketanserin, a 5-HT2-receptor antagonist on the impaired blood cell filtration in patients with acute myocardial infarction’, Clin. Haemorheol. 5, 949–957.
De Cree, J., Leempoels, J., Demoen, B., Roels, V. and Verhaegen, H. (1985a) ‘Effect of ketanserin in the hyperreactivity of platelets to 5-hydroxytryptamine in patients with cardiovascular diseases’, J. Cardiovasc. Pharmacol. 7, S26–S28.
De La Lande, I. S., Cannel, V. A. and Waterson, J. G. (1966) ‘The interaction of serotonin and noradrenaline on the perfused artery’, Br. J. Pharmacol. Chemother. 28, 255–272.
DeMey, C. and Vanhoutte, P. M. (1981) ‘Effect of age and spontaneous hypertension on the tachyphylaxis to 5-hydroxytryptamine and angiotensin II in the isolated rat kidney’, Hypertension 3, 718–724.
Dormandy, J. A. (1985) ‘HemoTheological effects of serotonin and serotonergic antagonists’, in P. M. Vanhoutte (ed.), Serotonin and the Cardiovascular System, Raven Press, New York, pp. 179–188.
Doyle, E. A., Fraser, J. R. E. and Marshall, R. J. (1959) ‘Reactivity of forearm vessels to vasoconstrictor substances in hypertensive and normotensive subjects’, Clin. Sci. 18, 441–454.
Engel, G., Gothert, M., Miiller-Schweinitzer, E., Schlicker, E., Sistonen, L. and Stadler, P. A. (1983) ‘Evidence for common pharmacological properties of [3H]5-hydroxytryptamine binding sites, presynaptic 5-hydroxytryptamine autoreceptors in CNS and inhibitory presynaptic 5-hydroxytryptamine receptors on sympathetic nerves’, Naunyn Schmiedebergs Arch. Pharmacol. 324, 116–124.
Flavahan, N. A., Shimokawa, H. and Vanhoutte, P. M. (1989) ‘Pertussis toxin inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries’, J. Physiol. 408, 549–560.
Forster, C., Whalley, E. T., Mohan, J. and Dutton, J. (1980) ‘Vascular smooth muscle response to fibrinogen degradation products and 5-hydroxytryptamine: Possible role in cerebral vasospasm in man’, Br. J. Clin. Pharmacol. 10, 231–236.
Garland, C. J. (1985) ‘Endothelial cells and the electrical and mechanical responses of the rabbit coronary artery to 5-hydroxytryptamine’, J. Pharmacol. Exp. Ther. 233, 158–162.
Gershon, M. D. and Tamir, H. (1985) ‘Peripheral sources of serotonin and serotonin-binding proteins’, in P. M. Vanhoutte (ed.), Serotonin and the Cardiovascular System, Raven Press, New York, pp. 15–26.
Gillis, C. N. (1985) ‘Peripheral metabolism of serotonin’, in P. M. Vanhoutte (ed.), Serotonin and the Cardiovascular System, Raven Press, New York, pp. 27–36.
Glusa, E. and Markwardt, F. (1984) ‘Inhibition of 5-hydroxytryptamine-potentiated aggregation of human blood platelets by 5-hydroxytryptamine-blocking agents’, Biomed. Biochim. Acta. 43, 215–220.
Golino, P., Buja, L. M., Ashton, J. H., Kulkarni, P., Taylor, A. and Willerson, J. T. (1988a) ‘Effect of thromboxane and serotonin receptor antagonists on intracoronary platelet deposition in dogs with experimentally stenosed coronary arteries’, Circulation 78, 701–711.
Golino, P., Ashton, J. H., Glas-Greenwalt, P., McNatt, J., Buja, L. M. and Willerson, J. T. (1988) ‘Mediation of reocclusion by thromboxane A2 and serotonin after thrombolysis with tissue-type plasminogen activator in a canine preparation of coronary thrombosis’, Circulation 77, 678–684.
Haeusler, G. and Finch, L. (1972) ‘Vascular reactivity to 5-hydroxytryptamine and hypertension in the rat’, Naunyn Schmiedebergs Arch. Pharmacol. 272, 101–116.
Heistad, D. D., Armstrong, M. L., Marcus, M. L., Piegors, D. J. and Mark, A. L. (1984) ‘Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys’, Circ. Res. 54, 711–718.
Hogan, J. C., Lewis, M. J. and Henderson, A. J. (1988) ‘In vivo EDRF activity influences platelet function’, Br. J. Pharmacol. 94, 1020–1022.
Hollenberg, N. K. (1985) ‘Segmental vascular responses to serotonin’, in P. M. Vanhoutte (ed.), Serotonin and the Cardiovascular System, Raven Press, New York, pp. 165–170.
Houston, D. S., Shepherd, J. T. and Vanhoutte, P. M. (1985) ‘Adenine nucleotides, serotonin and endothelium-dependent relaxations to platelets’, Am. J. Physiol. 248, H389 - H395.
Houston, D. S. and Vanhoutte, P. M. (1986) ‘Serotonin and the vascular system. Role in health and disease, and implications for therapy’, Drugs 31, 149–163.
Humphrey, W. R. and Aiken, J. W. (1982) ‘Antithrombotic and hypotensive effects of the serotoni receptor antagonist ketanserin in anesthetized dogs’, Pharmacologist 24, 196.
Janssens, W. J. and Van Nueten, J. M. (1986) ‘The direct and amplifying effects of serotonin are increased with age in the isolated perfused kidney of Wistar and spontaneously hypertensive rats’, Naunyn Schmiedebergs Arch. Pharmacol. 334, 327–332.
Kubo, T. and Su, C. (1983) ‘Effects of serotonin and some other neurohumoral agents on adrenergic neurotransmission in spontaneously hypertensive rat vasculature’, Clin. Exp. Hypertens. (A) 5, 1501–1510.
Lamping, K. G. and Dole, W.P. (1987) ‘Acute hypertension selectively potentiates constrictor responses of large coronary arteries to serotonin by altering endothelial function in vivo’. Circ. Res. 61, 904–913.
Lorenz, R. R. and Vanhoutte, P. M. (1984) ‘Aggregating platelets and adrenergic neurotransmission in isolated canine blood vessels’, Fed. Proc. 43, 430.
Lüscher, T. F. (1988) Endothelial vasoactive substances and cardiovascular disease, Karger, Basel.
Macdonald, P. S., Read, M. A. and Dusting, G. J. (1988) ‘Synergistic inhibition of platelet aggregation by endothelium-derived relaxing factor and prostacyclin’, Thromb. Res. 49, 437–449.
Marwood, J. F. and Stokes, G. S. (1984) ‘Serotonin (5HT) and its antagonists: Involvement in the cardiovascular system’, Clin. Exp. Pharmacol. Physiol. 11, 439–455.
McGrath, M. A. (1977) ‘5-Hydroxytryptamine and neurotransmitter release in canine blood vessels’, Circ. Res. 41, 428–435.
McGregor, D. D., Smirk, F. H. (1970) ‘Vascular responses to 5-hydroxytryptamine in genetic and renal hypertensive rats’, Am. J. Physiol. 219, 687–690.
Mecca, T. E., Mitchell, J., Bohr, D. F., Webb, R. C. (1985) ‘Effects of serotonin antagonists on blood pressure in mineralocorticoid hypertensive sheep’, J. Cardiovasc. Pharmacol. 7, 660–665.
Meyers, J. H., Mecca, T. E., Webb, R. C. (1985) ‘Direct and sensitizing effects of serotonin agonists and antagonists on vascular smooth muscle’, J. Cardiovasc. Pharmacol. 7 (Suppl. 7), S44–S48.
Moncada, S., Vane, J. R. (1979) ‘The role of prostacyclin in vascular tissue’, Fed. Proc. 38, 66–71.
Mullane, K. M., Bradley, G. and Moncada, S. (1982) ‘The interactions of platelet-derived mediators on isolated canine coronary arteries’, Eur. J. Pharmacol. 84, 115–118.
Nevelsteen, A., De Clerck, F., Loots, W., De Gryse, A. (1984) ‘Restoration of post-thrombotic peripheral collateral Circulation in the cat by ketanserin, a selective 5-HT2 receptor antagonist’, Arch. Int. Pharmacodyn. Ther. 270, 268–274.
Paiva, M. Q., Caramona, M., Osswald, W. (1984) ‘Intraand extraneuronal metabolism of 5-hydroxytryptamine in the isolated saphenous vein of the dog’, Naunyn Schmiedebergs Arch. Pharmacol. 325, 62–68.
Rapport, M. M., Green, A. A., Page, I. H. (1948) ‘Serum vasoconstrictor (serotonin). IV. Isolation and characterization’, J. Biol. Chem. 176, 1243.
Radomski, M. W., Palmer, R. M. J., Moncada, S. (1987) ‘Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets’, Br. J. Pharmacol. 92, 181–187.
Radomski, M. W., Palmer, R. M. J., Moncada, S. (1987) ‘Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium’, The Lancet 2, 1057–1058.
Ross, R. (1987) ‘Growth factors in the pathogenesis of atherosclerosis’, Acta Med. Scand. 715, 33–38.
Shimokawa, H., Aarhus, L. L., Vanhoutte, P. M. (1987) ‘Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin’, Circ. Res. 61, 256–270.
Shimokawa, H., Aarhus, L. L., Vanhoutte, P. M. (1987) ‘Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin’, Circ. Res. 61, 256–270.
Sneddon, J. M., Vane, J. R. (1988) ‘Endothelium-derived relaxing factor reduces platelet adhesion to bovine endothelial cells’, Proc. Natl. Acad. Sci. 85, 2800–2804.
Stoltz, J. F. (1985) ‘Uptake and storage of serotonin by platelets’, in P. M. Vanhoutte (ed.), Serotonin and the Cardiovascular System, Raven Press, New York, pp. 37–42.
Toda, N., Bian, K., Inoue, S. (1987) ‘Age-related changes in the response to vasoconstrictor and dilator agents in isolated beagle coronary arteries’, Naunyn Schmiedebergs Arch. Pharmacol. 336, 359–364.
Toda, N., Hayashi, S. (1979) ‘Age-dependent alteration in the response of silated rabbit basilar arteries to vasoactive agents’, J. Pharmacol. Exp. Ther. 211, 716–721.
Vanhoutte, P. M. (1985) ‘Peripheral serotonergic receptors and hypertension’, in P. M. Vanhoutte (ed.), Serotonin and the Cardiovascular System, Raven Press, New York, pp. 123–133.
Vanhoutte, P. M., Houston, D. S. (1985) ‘Platelets, endothelium, and vasospasm’, Circulation 72, 728–734.
Vanhoutte, P. M., Verbeuren, T. J. Webb, R. C. (1981) ‘Local modulation of the adrenergic neuroeffector interaction in the blood vessel wall’, Physiol. Rev. 61, 151–247.
Van Nueten, J. M. (1982) ‘Serotonergic amplification mechanisms in vascular tissues’, in F. De Clerck and P. M. Vanhoutte (eds.), 5-hydroxytryptamine in Peripheral Reactions, Raven Press, New York, pp. 77–82.
Van Nueten, J. M., Janssen, P. A. J., De Ridder, W., Vanhoutte, P. M. (1982) ‘Interaction between 5-hydroxytryptamine and other vasoconstrictor substances in the isolated femoral artery of the rabbit: Effect of ketanserin (R 41 468)’, Eur. J. Pharmacol. 77, 281–287.
Van Nueten, J. M., Janssen, P. A. J., Van Beek, J., Xhonneux, R., Verbeuren, T. J., Vanhoutte, P. M. (1981) ‘Vascular effects of ketanserin (R 41 468), a novel antagonist of 5-HT2 serotonergic receptors’, J. Pharmacol. Exp. Ther. 218, 217–230.
Van Nueten, J. M., Janssens, W. J., Vanhoutte, P. M. (1985) ‘Serotonin and vascular smooth muscle’, in P. M. Vanhoutte (ed.), Serotonin and the Cardiovascular System, Raven Press, New York, pp. 95–104.
Van Nueten, J. M., Leysen, J. E. De Clerck, F., Vanhoutte, P. M. (1984) ‘Serotonergic receptor subtypes and vascular reactivity’, J. Cardiovasc. Pharmacol. 6, 5564–5574.
Verbeuren, T. J., Jordaens, F. H., Herman, A. G. (1983) ‘Accumulation and release of [3H]–5-hydroxytryptamine in saphenous veins and cerebral arteries of the dog’, J. Pharmacol. Exp. Ther. 226, 579–588.
Verbeuren, T. J., Jordaens, F. H., Zonnekeyn, L. L., Van Hove, C. E., Coene, M. C., Herman, A. G. (1986) ‘Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits’, Circ. Res. 58, 552–564.
Verheyen, A., Vlaminckx, E., Lauwers, F., Van den Broeck, C., Wouters, L. (1984) ‘Serotonin-induced blood flow changes in the rat hindlegs after unilateral ligation of the femoral artery: inhibition by the S2-receptor antagonist ketanserin’, Arch. Int. Pharmacodyn. Ther. 270, 280–298.
Webb, R. C., Vanhoutte, P. M. (1985) ‘Responsiveness of the hypertensive blood vessel wall to serotonergic stimuli’, in P. M. Vanhoutte (ed.), Serotonin and the Cardiovascular System, Raven Press, New York, pp. 113–121.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Kluwer Academic Publishers
About this chapter
Cite this chapter
Vanhoutte, P.M., Van Nueten, J.M., Janssens, W.J. (1990). The Role of the Endothelium in the Cardiovascular Response to Serotonin. In: Paoletti, R., Vanhoutte, P.M., Brunello, N., Maggi, F.M. (eds) Serotonin. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-1912-9_12
Download citation
DOI: https://doi.org/10.1007/978-94-009-1912-9_12
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-7353-0
Online ISBN: 978-94-009-1912-9
eBook Packages: Springer Book Archive