The Effect of Serotonin Inhibition on Initial Microvessel Hemostasis and Platelet Aggregation In Vivo

D Bergqvist; S Arvidsson; C O Esquivel; B Lindblad; U Haglund

doi:10.1055/s-0038-1657355

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1983; 49(03): 173-175
DOI: 10.1055/s-0038-1657355

Original Article

Schattauer GmbH Stuttgart

The Effect of Serotonin Inhibition on Initial Microvessel Hemostasis and Platelet Aggregation In Vivo

Authors

D Bergqvist

The Departments of Surgery and Experimental Research, Malmö General Hospital, Malmö and Department of Experimental Medicine, Pharmacia AB, Uppsala, Sweden
S Arvidsson

The Departments of Surgery and Experimental Research, Malmö General Hospital, Malmö and Department of Experimental Medicine, Pharmacia AB, Uppsala, Sweden
C O Esquivel

The Departments of Surgery and Experimental Research, Malmö General Hospital, Malmö and Department of Experimental Medicine, Pharmacia AB, Uppsala, Sweden
B Lindblad

The Departments of Surgery and Experimental Research, Malmö General Hospital, Malmö and Department of Experimental Medicine, Pharmacia AB, Uppsala, Sweden
U Haglund

The Departments of Surgery and Experimental Research, Malmö General Hospital, Malmö and Department of Experimental Medicine, Pharmacia AB, Uppsala, Sweden

Abstract

PDF Download

Summary

The role of serotonin (5-HT) in initial microvascular hemostasis is not fully understood. This study was made to evaluate the effect on hemostatic plug formation and laser-induced arteriolar microembolism of different substances which counteract the effect of 5-HT. Hemostatic plug formation time and stability was measured in the rabbit mesenteric microcirculation and laserinduced embolism in the rabbit ear chamber. Ketanserine, a selective 5-HT₂-receptor blocker shortened arteriolar hemostatic plug formation time. Dihydroergotamine, an unselective blocker (with 5-HT- and α-adrenergic receptor affinity) increased venular hemostatic plug formation time and also decreased the hemostatic plug stability. Laser-induced platelet embolism was unaltered after both ketanserine and dihydroergotamine administration. The magnitude of these changes seems to exclude an important effect of 5-HT in initial microvessel hemostasis or on platelet activity.

Keywords

Rabbits - Hemostatic plug - Platelet - Ketanserine - Dihydro - ergotamine

PDF (1097 kb)

References

References
1 Holmsen H. Biochemistry of the platelet release reaction. In: Biochemistry and Pharmacology of Platelets. Ciba Foundation Symposium 35. Elsevier. North Holland Biomedical Press; Amsterdam: 1975. pp. 175-205
2 Bergqvist D. Haemostatic plug formation in the rabbit mesentery. A methodological study. Ups J Med Sci 1974; 79: 28-38
3 McKenzie FN, Arfors K-E, Matheson NA. Measurement of the platelet response to laser-induced microvascular injury. Assessment of determinants of platelet aggregation in vivo. Thrombos Diathes Haemorrh 1974; 32: 704-713
4 Leysen JE, Amouters F, Kennis L, Landron PM, Vandeberk J, Janssen PA J. Receptor binding profile of R 41468, a novel antagonist at 5-HT₂-receptors. Life Sci 1981; 28: 1015-1022
5 Salzmann R, Bucher T. Actions of ergot alkaloids on adrenoreceptors. In: Ergot alkaloids and related compounds. Berde B, Schild HO. (Eds) Springer-Verlag; Berlin, Heidelberg, New York: 1978: 140-177
6 Arfors K-E, Bergqvist D, McKenzie FN, Nilsson G. Platelet response to laser induced microvascular injury in the rabbit mesentery and the rabbit ear chamber. A statistical comparison. Thromb Res 1973; 3: 75-85
7 Bergqvist D, Arfors K-E. Influence of platelet count on haemostatic plug formation and plug stabilit. An experimental study in rabbits with graded thrombocytopenia. Thrombos Diathes Haemorrh 1973; 30: 586-596
8 Bergqvist D, Arfors K-E. Influence of fibrinolysis and coagulation on haemostatic plug formation. An experimental study in rabbits. Thromb Res 1974; 4: 345
9 Bergqvist D. Haemostatic plug formation time and stability in the microvasculature of rabbit mesentery. Acta Univ Ups 167, Abstract of Uppsala Dissertations from the faculty of medicine. 1973
10 Arfors K-E, Artursson G, Bergqvist D, Svensjö E. The effect of inhibition of prostaglandin synthesis on microvascular haemostasis and macromolecular leakage. Thromb Res 1976; 8: 393-402
11 Hovig T, McKenzie FN, Arfors K-E. Measurement of the platelet response to laser-induced microvascular injury. Ultrastructural studies. Thrombos Diathes Haemorrh 1974; 32: 695-703
12 van Neuten JM, Janssen P, van Beek J, Xhonneux R, Verbeuren TJ, Vanhoutte P. Vascular effects of Ketanserine (R 41468): A novel antagonist of %-HT₂ serotonergic receptors. J Pharmacol Exp Ther 1981; 218: 217-230
13 DeClerck F, David J-L, Janssen PA J. Inhibition of 5-Hydroxytryptamine-induced and amplified human platelet aggregation by Ketanserine (R 41468), a selective 5-HT₂ receptor antagonist. Agents and Actions. (in press).
14 Bergqvist D, McKenzie FN, Arfors K-E. Influence of different anaesthetic agents on the formation and stability of haemostatic plug in the rabbit mesentery. Ups J Med Sci 1974; 79: 39-44
15 Arvidsson S, Bergqvist D, Esquivel CO, Lindblad B, Haglund U. Hemodynamic effects of dihydroergotamine and ketanserine in E. Coli bacteriemic shock. Scand J Lab Invest. In press.
16 Bergqvist D, Arfors K-E. Haemostasis in the microvasculature of the rabbit mesentery; Effects of some pharmacological agents of current interest in haemostasis and thrombosis. Haemostasis 1976; 5: 74-84
17 Arfors K-E, Bergqvist D. Platelet aggregability and vessels contraction in microvascular haemostasis. Microvasc Res 1975; 9: 22-28
18 Reimer H-J, Packham M, Cazenave J-P, Mustard JF. Effect of reserpine on adenosine uptake and metabolism and subcellular transport of platelet adenosine triphosphate in washed rabbit platelets. Biochem Pharmacol 1977; 26: 1657-1665
19 Reimers H-J, Allen D, Cazenave J-P, Feuerstein I, Mustard JF. Serotonin transport and storage in rabbit blood platelets – the effect of reserpine and imipramine. Biochem Pharmacol 1977; 26: 1645-1655
20 Kakkar VV. Knowledge and prospective of thromboembolic research. In: Postoperative Thromboemboli-Prophylaxe aus aktueller Sicht. Tscheme H, Deutsch E. (Eds) Georg Thieme Verlag. pp 1-6 Stuttgart; New York: 1981
21 Born GV R, Bergqvist D, Arfors K-E. Evidence for inhibition of platelet activation in blood by a drug effect on erythrocytes. Nature 1976; 259: 233-235
22 Bergqvist D, Arfors K-E. Haemostatic platelet plug formation in the isolated rabbit mesenteric preparation – an analysis of red blood cell participation. Thromb Haemostas 1980; 44: 6-8
23 De Gaetano G. Platelets prostaglandins and thrombotic disorders. In: Thrombosis. Clinics in haematology. Prentice CRM. (Ed). W B Saunders Comp. Ltd; London, Philadelphia, Toronto: 1981. 10. 2: 297-326
24 Sagar S, Stamatakis JD, Higgins AF, Nim D, Maffei FH, Thomas DP, Kakkar VV. Efficacy of low-dose heparin in prevention of extensive deep-vein thrombosis in patients undergoing total hip replacement. Lancet 1976; 01: 1151-1154
25 Bergqvist D, Efsing HO, Hallböök T, Lindblad B. Prevention of postoperative thromboembolic complications. A prospective comparison between dextran 70, dihydroergotamine heparin and a sulphated polysaccharide. Acta Chir Scand 1980; 146: 559-568
26 Gruber UF. Prevention of tatal postoperative pulmonary embolism by heparin dihydroergotamine or dextran 70. Br J Surg 1982; 69: 54-58
27 Barthel W, Markwardt F. Aggregation of blood platelets by biogenic amines and its inhibition by antiadrenergic and antiserotoninergic agents. Biochem Pharmacol 1974; 23: 37-45
28 Lindblad B, Bergqvist D, Hedner U. The effects of dihydroergotamine on the haemostatic system. Thromb Haemostas 1983; 50 (Abstr.).