Platelet Aggregation and In Vivo Shear Forces

Summary

Haemodynamic shear forces have been reported to exert direct and indirect effects on platelet reactivity. In vitro, they activate platelets leading to spontaneous or facilitated aggregation. In vivo, they stimulate the production of endothelium-derived antiaggregatory agents. This study was designed to evaluate in hypertensive patients, before and after antihypertensive treatment, the possible role of these haemodynamic forces, determined at the brachial artery level on the ex vivo platelet aggregatory response to ADP and collagen. Platelet reactivity, evaluated by EC₅₀ for ADP and collagen, was found to be related to blood velocity, shear rate and shear stress (p <0.01 for each). These inverse correlations of platelet aggregation with stress levels did not depend on age, body mass index, mean blood pressure, serum cholesterol and triglycerides or haematocrit. They were also independent of platelet cytosolic Ca²⁺ and cyclic AMP.

The changes in shear forces and in aggregatory responses to ADP and collagen induced by nitrendipine treatment for 6 months remained negatively correlated, confirming the relationships existing between haemodynamic shear forces and platelet reactivity.

These results indicate that the shear antiaggregant effects, likely mediated by tlow-dependent endothelium-derived factors, prevail over its direct platelet aggregating effects.

• References

• 1 Gear AR L. Rapid platelet morphological changes visualized by scanning-electron microscopy: kinetics derived from a quenched-flow approach. British J Haematol 1984; 56: 387-98
• 2 O’Brien JR. Shear-induced platelet aggregation. Lancet 1990; 335: 711-3
• 3 Yung W, Frojmovic MM. Platelet aggregation in laminar flow. I. Adenosine diphosphate concentration, time and shear rate dependence. Thromb Res 1982; 28: 361-77
• 4 Bell DN, Spain S, Goldsmith HL. Adenosine diphosphate-induced aggregation of human platelets in flow through tubes. II. Effect of shear rate, donor sex and ADP concentration. Biophys J 1989; 56: 829-43
• 5 Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Anbo H, Kawai Y, Watanabe K, Itagaki I, Sakai K, Ruggieri ZM. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying stress. J Clin Invest 1991; 87: 1234-40
• 6 Baumgartner HR, Turitto V, Weiss HJ. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. J Lab Clin Med 1980; 95: 208-21
• 7 Olson JD, Zaleski A, Herrmann D, Flood PA. Adhesion of platelets to purified solid-phase von Willebrand faetoi. Effccb uf wall slieax rate, ADP, thrombin and ristocetin. J Lab Clin Med 1989; 114: 6-18
• 8 Giorgio TD, Heliums JD. A cone and plate viscometer for the continuous measurement of blood platelet activation. Biorheology 1988; 25: 605-24
• 9 Kawakami K, Fukuyama M, Sakai K, Itagaki I, Kawano K, Handa M, Ikeda Y. Change in intracellular calcium during shear induced platelet aggregation. ASAIO Trans 1990; 36: M696-9
• 10 Moritz MW, Reimers RC, Baker RK, Sutera SP, Joist JH. Role of cytoplasmic and releasable ADP in platelet aggregation induced by laminar shear stress. J Lab Clin Med 1983; 101: 537-44
• 11 Wurzinger LJ, Opitz R, Blassberg P, Schmid-Schonbein H. Platelet and coagulaton parameters following millisecond exposure to laminar shear stress. Thromb Haemost 1985; 54: 381-6
• 12 Kroll MH, Heliums JD, Guo Z, Durante W, Razdan K, Hrbolich JK, Schafer AI. Protein kinase C is activated in platelets subjected to pathological shear stress. J Biol Chem 1993; 268: 3520-4
• 13 Schwartz CJ, Sprague EA. Vascular endothelium and hemodynamic stress. Nutr Metab Cardiovasc Dis 1992; 2: 99-100
• 14 Larsen FL, Katz S, Roufogalis BD, Brookst DE. Physiological shear stresses enhance the Ca²⁺ permeability of human erythrocytes. Nature 1981; 294: 667-8
• 15 Frangos JA, Eskin SG, Mclntire LV. Flow effects on prostacyclin production by cultured human endothelial cells. Science 1985; 227: 1477-9
• 16 Grabovski EF, Jaffe EA, Weksler BB. Prostacyclin production by cultured endothelium cell monolayers exposed to step increases in shear stress. J Lab Clin Med 1985; 105: 36-43
• 17 Rubanyi GM, Vanhoutte PM. Oxygen-derived free radicals, endothelium and responsiveness of vascular smooth muscle. Am J Physiol 1986; 250: H822-7
• 18 Yoshizumi M, Kurihara H, Sugiyama T, Takaku F, Yanagisawa M, Masaki T, qYazaki Y. Hemodynamic shear stress stimulates endothelin production by cultured endothelium cells. Biochem Biophys Res Commun 1989; 161: 859-64
• 19 Milner P, Bodin P, Loesch A, Burnstock G. Rapid release of endothelin and ATP from isolated aortic endothelial cells exposed to increased flow. Biochem Biophys Res Commun 1990; 649-56
• 20 Nollert MU, Diamond SK, Mc Intyre LV. Hydrodynamic shear stress and mass transport modulation of endothelial cell metabolism. Biotechnol Bioeng 1991; 38: 588-602
• 21 Radomski MW, Palmer RM J, Moncada S. The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol 1987; 92: 639-46
• 22 Astarie-Dequeker C, Iouzalen L, David-Dufilho M, Devynck M-A. In vitro inhibition by endothelins of thrombin-induced aggregation and Ca²⁺ mobilization in human platelets. Br J Pharmacol 1992; 106: 966-71
• 23 Diamond SL, Eskin SG, Mclntire LV. Fluid flow stimulates tissue plasminogen activator secretion by cultured human endothelium cells. Science 1989; 243: 1483-5
• 24 Simon A, Levenson J. Abnormal wall shear conditions in the brachial artery of hypertensive patients. J Hypertens 1990; 8: 109-14
• 25 Badimon JJ, Badimon L, Turitto VT, Fuster V. Platelet deposition at high shear rates is enhanced by high plasma cholesterol levels. Arterioscler Thromb 1991; 11: 395-402
• 26 Carvalho AC A, Colman RW, Lees RS. Platelet function in hyperlipoproteinemia. N Engl J Med 1974; 290: 434-8
• 27 Tremoli E, Maderna P, Colli S, Morazzoni G, Sirtori M, Sirtori CR. Increased platelet sensitivity and thromboxane B₂ formation in type-II hyperlipoproteinaemic patients. Eur J Clin Invest 1984; 14: 329-33
• 28 Ellefson RD, Caraway WT. Blood lipids. In: Fundamentals of clinical chemistry. Trietz NM. (ed.) WB Saunders Co; Philadelphia: 1982: 509-10
• 29 Simon A, Levenson J, Cambien F, Bouthier J. Combined effects of gender and hypertension on the geometric design of large arteries. Sexual differences in normal and hypertensive forearm arteries. Am J Hypertens 1988; 1: 119-23
• 30 Simon A, Flaud P, Levenson J. Pulsatile flow and oscillating wall shear stress in the brachial artery of normotensive and hypertensive subjects. Cardiovasc Res 1990; 2: 129-36
• 31 Levenson J, Simon A, Cambien F, Beretti C. Cigarette smoking and hypertension: factors independently associated with blood hyperviscosity and arterial rigidity. Arteriosclerosis 1987; 2: 572-7
• 32 Levenson J, Simon A, Pithois-Merli I. Brachial arterial changes in wrist exclusion in normotensive and hypertensive men. Am J Physiol 1987; 253: H217-H224
• 33 Born GV R. Aggregation of blood platelets by adenosine and its reversal. Nature 1962; 195: 927-9
• 34 Le Quan Sang KH, Devynck MA. Increased platelet cytosolic free calcium concentration in essential hypertension. J Hypertension 1986; 4: 567-74
• 35 Mazeaud MM, Le Quan Sang KH, Devynck MA. Platelet cyclic AMP in essential hypertension. J Hypertens 1989; 7: 501-6
• 36 Moncada S, Gryglewski RT, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxydes to an unstable substance that inhibits platelet aggregation. Nature 1976; 263: 663-5
• 37 Azuma H, Ishikawa M, Sekisaki S. Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol 1986; 88: 411-5
• 38 Johnson M, Ramey E, Ramwell PW. Sex and age differences in human platelet aggregation. Nature 1975; 253: 355-7
• 39 Mazeaud MM, Driss F, Le Quan Sang KH, Duranthon V, Levenson J, Simon A, Devynck MA. Biochemical and functional alterations associated with hypercholesterolemia in platelets from hypertensive patients. Atherosclerosis 1992; 94: 201-11
• 40 Rink TJ, Smith SW, Tsien RY. Cytosolic free Ca²⁺ in human platelets: Ca²⁺ threshold and Ca²⁺-independent activation for shape-change and secretion. FEBS Lett 1982; 148: 21-6
• 41 Siess W. Molecular mechanisms of platelet activation. Physiol Rev 1989; 69: 58-178
• 42 Nyrop M, Zweifler AJ. Platelet aggregation in hypertension and the effects of antihypertensive treatment. J Hypertens 1988; 6: 263-9
• 43 Blache D, Ojeda C. Comparative inhibitory effects of dihydropyridines on platelet aggregation, calcium uptake and cyclic AMP concentration. Pharmacology 1992; 45: 250-9
• 44 Godfraind T, Miller R, Wibo M. Calcium antagonism and calcium entry blockade. Pharmacol Rev 1986; 38: 321-416
• 45 Zschauer A, Van Breemer C, Biihler FR, Nelson MT. Calcium channels in thrombin-activated human platelet membrane. Nature 1988; 334: 703-5
• 46 Vanhoutte PM. Role of calcium and endothelium in hypertension, cardiovascular disease, and subsequent vascular events. J Cardiovasc Pharmacol 1992; 19 Suppl. (Suppl. 03) S6-S10