Effects of Bupranolol, a New β-Blocker, on Platelet Functions of Rabbit and Human in Vitro

Teruhiko Umetsu; Kazuko Sanai; Tadakatsu Kato

doi:10.1055/s-0038-1648052

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1976; 36(02): 376-387
DOI: 10.1055/s-0038-1648052

Original Article

Schattauer GmbH

Effects of Bupranolol, a New β-Blocker, on Platelet Functions of Rabbit and Human in Vitro

Authors

Teruhiko Umetsu

¹Research Laboratory, Kaken Chemical Co., Ltd., Honkomagome 2–28–8, Bunkyo-ku, Tokyo, Japan
Kazuko Sanai

¹Research Laboratory, Kaken Chemical Co., Ltd., Honkomagome 2–28–8, Bunkyo-ku, Tokyo, Japan
Tadakatsu Kato

¹Research Laboratory, Kaken Chemical Co., Ltd., Honkomagome 2–28–8, Bunkyo-ku, Tokyo, Japan

Abstract

Summary

The effects of bupranolol, a new β-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known β-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased.

Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4–3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the β-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8–3.3 times as effectively as propranolol.

From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis.

Full Text

References

References
1 Abudulla Y. H. 1969; β-Adrenergic receptors in human platelets. Journal of Atherosclerosis Research 9: 171.
2 Barthel W, Markwardt F. 1974; Aggregation of blood platelets by biogenic amines and its inhibition by anti-adrenergic and anti-serotoninergic agents. Biochemical Pharmacology 23: 37.
3 Born G. V. R. 1962; Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194: 972.
4 Brecher G, Cronkite E. P. 1950; Morphology and enumeration of human blood platelets. Journal of Applied Physiology 3: 365.
5 Bygdeman S, Johnson O. 1969; Studies on the effect of adrenergic blocking drugs on catecholo-mine-induced platelet aggregation and uptake of noradrenaline and 5-hydrosytryptamine. Acta Phy-siologica Scandinavia 75: 129.
6 Dreyfuss F, Zahavi J. 1973; Adenosine diphosphate induced platelet aggregation in myocardial infarction and ishemic heart disease. Atherosclerosis 17: 107.
7 Gibelli G, Montanari C, Bellan D, Mandelli V, Sacchetti G. 1973; Beta-blocking drugs and human platelet aggregation in vitro. Experientia 29: 186.
8 Haerem J. W. 1974; Mural platelet microthrombi and major acute lesions of main epicardial arteries in sudden coronary death. Atherosclerosis 19: 529.
9 Haft J.L, Gershengorn K, Kranz P. D, Oestreicher R. 1972a Protection against epinephrine-induced myocardial necrosis by drugs that inhibit platelet aggregation. American Journal of Cardiology 30: 838.
10 Haft J. I, Kranz P. D, Albert F. J, Fani K. 1972b Intravascular platelet aggregation in the heart induced by norepinephrine. Microscopic studies. Circulation 46: 698.
11 Lemmer B, Wiethold G, Hellenbrecht D, Bak I. J, Grobcker H. 1972; Human blood platelets as cellular models for investigation of membrane active drugs: Beta-adrenergic blocking agents. Naunyn-Schmiedeberg’s Archiv für Pharmakologie 275: 299.
12 Matsuda T. 1973; Arteriosclerosis and thrombosis. Rinsho Byori 21: 886.
13 McNicol G. P, Mitchell J. R. A, Reuter H, Loo J. V. D. 1974; Platelets in thrombosis. Their clinical significance and the evaluation of potential drugs. Thrombosis et Diathesis Haemorrhagica 31: 379.
14 Mills D. C. B, Roberts G. C. K. 1967; Effects of adrenaline on human blood platelets. Journal of physiology 193: 443.
15 O’Brien J. R, Etherington M, Jamieson S, Klaber M. R, Lincoln S. V. 1974; Platelets function long after arterial and venous thrombosis. Thrombosis et Diathesis Haemorrhagica 31: 279.
16 Salzman E. W. 1963; Measurement of platelet adhesiveness. A simple in vitro technique demonstrating an abnormality in von Willebrand’s disease. Journal of Laboratory and Clinical Medicine 62: 724.
17 Sano T, Yokoyama M. 1971; Effect of pyridinolcarbamate on platelet aggregation. American Journal of Medical Sciences 262: 205.
18 Shimamoto T, Yamazaki H, Inoue M, Fujita T, Sagawa N, Ishioka T, Sunaga T. 1960; Effect of adrenaline and noadrenaline on “silicone-like property” of blood vessels. Proceedings of the Japan Academy 36: 234.
19 Shimamoto T. 1963; The relationship of edematous reaction in arteries to atherosclerosis and thrombosis. Journal of Atherosclerosis Research 3: 87.
20 Sinakos Z, Caen J. P. 1967; Platelet aggregation in mammalians (human, rat, rabbit, guineapig, horse, dog). A comparative study. Thrombosis et Diathesis Haemorrhagica 17: 99.
21 Spaet T. H, Stemerman M. B. 1972. Platelet adhesion. In: Weiss H. J. (ed). Platelets and their Role in Hemostasis. Annals of New York Academy of Sciences. 201 13.
22 Umetsu T, Kato T. 1973; Biochemical studies on a new β-receptor blocking agent, l-(tert-butylamino)-3-(2-chloro-5-methylphenoxy)-2-propanol (2) Effect of KL 255 on ADP-induced rabbit platelet aggregation. Pharmacometrics 7: 31.
23 Yamazaki H, Odakura T, Takeuchi K, Sano T. 1970; Adhesive platelet count and blood coagulability in myocardial infarction and cerebral thrombosis. Thrombosis et Diathesis Haemorrhagica 24: 450.
24 Yamazaki H, Sano T, Odakura T, Takeuchi K, Matsumura T, Hosaki S, Shimamoto T. 1971; Appearance of thrombogenic tendency induced by adrenaline and its prevention by β-adrenergic blocking agent, nialamide and pyridinolcarbamate. Thrombosis et Diathesis Haemorrhagica 26: 251.
25 Yamazaki H, Kobayashi L, Sano T, Shimamoto T. 1973; Enhancement of ADP-induced platelet aggregation by adrenaline in vivo and its prevention. Thrombosis et Diathesis Haemorrhagica 29: 490.
26 Yamazaki H. 1973; Platelet functions in thromboembolic disorders. Rinsho Byori 21: 892.