Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

Summary

The significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

• REFERENCES

• 1 O’Brien JR. Some effects of adrenaline and anti-adrenaline compounds on platelets in vitro and in vivo. Nature 1963; 200: 763-764
• 2 Lanza F, Bertz A, Stierlé A, Hanau D, Kubina M, Cazenave JP. Epinephrine potentiates human platelet activation but is not an aggregating agent. Am J Physiol 1988; 255: H1276-H1288
• 3 Larsson PT, Hjemdahl P, Olsson G, Egberg N, Hornstra G. Altered platelet function during mental stress and adrenaline infusions in humans: evidence for an increased in vivo aggregability as measured by filtragometry. Clin Sci 1989; 76: 369-376
• 4 Larsson PT, Hjemdahl P, Olsson G, Angelin B, Hornstra G. Platelet aggregability in humans: contrasting in vivo and in vitro findings during sympatho-adrenal activation and relationship to serum lipids. Eur J Clin Invest 1990; 20: 398-405
• 5 Larsson PT, Wallén NH, Egberg N, Hjemdahl P. α-Adrenoceptor blockade by phentolamine inhibits adrenaline-induced platelet activation in vivo without affecting resting measurements. Clin Sci 1992; 82: 369-376
• 6 Lande K, Gjesdal K, Fönstelien E, Kjeldsen SE, Eide I. Effects of adrenaline infusion on platelet number, volume and release reaction. Thromb Haemostas 1985; 54: 450-453
• 7 Laustiola K, Kaukinen S, Seppälä E, Jokela T, Vapaatalo H. Adrenaline infusion evokes increased thromboxane B₂ production by platelets in healthy men: the effect of beta-adrenoceptor blockade. Eur J Clin Invest 1986; 16: 473-479
• 8 Kerry R, Scrutton MC. Platelet adrenoceptors. In: The Platelets; Physiology and Pharmacology. Longenecker GL. (ed) Academic Press Inc, London: 1985. pp 113-185
• 9 Abdulla YH. β-Adrenergic receptors in human platelets. J Atheroscler Res 1969; 9: 171-177
• 10 Yu SK, Latour JG. Potentiation by α and inhibition by β-adrenergic stimulations of rat platelet aggregation. A comparative study with human and rabbit platelets. Thromb Haemostas 1977; 37: 413-421
• 11 Kerry R, Scrutton MC. Platelet β-adrenoceptors. Br J Pharmacol 1983; 79: 681-691
• 12 Burstein Y, Berns L, Heldenberg D, Kahn Y, Werbin BZ, Tamir I. Increase in platelet aggregation following a rise in plasma free fatty acids. Am J Hematol 1978; 4: 17-22
• 13 O’Brien J. Shear-induced platelet aggregation. Lancet 1990; 335: 711-713
• 14 Hjemdahl P. Physiology of the autonomic nervous system as related to cardiovascular function: implications for stress research. In: Anxiety and the Heart. Byrne DG, Rosenman RH. (eds) Hemisphere Publishing Corporation, New York: 1990. pp 095-158
• 15 Jern C, Eriksson E, Tengborn L, Risberg B, Wadenvik H, Jern S. Changes of plasma coagulation and fibrinolysis in response to mental stress. Thromb Haemostas 1989; 62: 767-771
• 16 Hawiger J. Adhesive interactions of blood cells and the vessel wall. In: Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds) J.B. Lippincott Company, Philadelphia, PA: 1987. pp 182-209
• 17 Sixma JJ, de Groot PG. Von Willebrand factor and the blood vessel wall. Mayo Clin Proc 1991; 66: 628-633
• 18 Hjemdahl P, Larsson PT, Wallén NH. Effects of stress and β-blockade on platelet function. Circulation 1991; 84 suppl 6 VI-44-VI-61
• 19 Beckmann ML, Gerber JG, Byyny RL, LoVerde M, Nies AS. Propranolol increases prostacyclin synthesis in patients with essential hypertension. Hypertension 1988; 12: 582-588
• 20 Hjemdahl P, Åkerstedt T, Pollare T, Gillberg M. Influence of β-adrenoceptor blockade by metoprolol and propranolol on plasma concentrations and effects of noradrenaline and adrenaline during i.v. infusion. Acta Physiol Scand 1983; 515 (suppl): 45-53
• 21 Hornstra G, ten Hoor F. The filtragometer: A new device for measuring platelet aggregation in venous blood of man. Thromb Diath Haemorrh 1975; 34: 531-544
• 22 Hornstra G. The filtragometer in thrombosis research. In: Platelet Function Testing. Day HJ, Holmsen H, Zucker MB. (eds) DHEW Publication no. (NIH) 78–1087 National Institutes of Health, Bethesda, MD: 1978. pp 416-427
• 23 Hjemdahl P, Perneby C, Theodorson E, Egberg N, Larsson PT. A new assay for β-thromboglobulin in urine. Thromb Res 1991; 64: 33-43
• 24 Hjemdahl P. Catecholamine measurements in plasma by high-performance liquid chromatography with electrochemical detection. Methods Enzymol 1987; 142: 521-534
• 25 Brown BL, Ekins RPZ, Albano JDM. Saturation assay for cyclic AMP using endogenous binding protein. Adv Cyclic Nucleotide Res 1972; 2: 25-40
• 26 Wadenvik H, Kutti J. The effect of an adrenaline infusion on the splenic blood flow and intrasplenic platelet kinetics. Br J Haematol 1987; 67: 187-192
• 27 Wadenvik H, Kutti J. The effect of an isoprenaline infusion on the splenic blood flow and intrasplenic platelet kinetics. Eur J Haematol 1987; 39: 07-13
• 28 Small M, Tweddel AC, Rankin AC, Lowe GDO, Prentice CRM, Forbes CD. Blood coagulation and platelet function following maximal exercise: Effects of beta-adrenoceptor blockade. Haemostasis 1984; 14: 262-268
• 29 Weksler BB, Gillick M, Pink J. Effect of propranolol on platelet function. Blood 1977; 49: 185-196
• 30 Frishman WH, Weksler BH, Christodoulou JP, Smithen C, Killip T. Reversal of abnormal platelet aggregability and change in exercise tolerance in patients, with angina pectoris following oral propranolol. Circulation 1974; 50: 887-896
• 31 Pamphilon DH, Boon RJ, Prentice AG, Rozkovec A. Lack of significant effect of therapeutic propranolol on measurable platelet function in healthy subjects. J Clin Pathol 1989; 42: 793-796
• 32 Laustiola K, Seppälä E, Nikkarai T, Vapaatalo H. Exercise-induced increase in plasma arachidonic acid and thromboxane B2 in healthy men: effect of β-adrenergic blockade. J Cardiovasc Pharmacol 1984; 6: 449-454
• 33 van Wyk V, du P Heyns A. Low molecular weight heparin as an anticoagulant for in vitro platelet function studies. Thromb Res 1990; 57: 601-609