Contribution of Platelets to the Cardiovascular Effects of ADP in the Rat

Summary

The contribution of platelets to the cardiovascular effects of ADP was investigated in rats in different experimental conditions. Following rapid i. v. bolus injections of ADP (from 0.001 to 0.03 mg/kg b. w.) only a dose-related fall in blood pressure could be detected. Increasing the dose of ADP (up to 1 mg/kg b. w.), platelet fall and changes in cardiac rhythm (bradycardia, A. V. blocks and ectopic beats) became evident. All these phenomena were rapidly reversed. Inhibition of platelet aggregation by a pyrimido-pyrimidine compound (SH 869) or thrombocytopenia induced by Busulfan or antiplatelet antiserum did not significantly protect the animals from the cardiovascular effects of ADP. The fall in blood pressure, however, was reduced. Adenosine, at equimolar concentrations, caused ECG changes similar to those induced by ADP with no platelet aggregation and a less pronounced blood pressure fall.

These results suggest that most of the cardiovascular modifications induced by rapid injection of ADP are largely independent of platelets. Platelets appeared to play a more important role when ADP was given for a longer period of time. A slow i. v. infusion of ADP (6 mg/kg b. w. for 10 min) was accompanied by platelet fall, cardiovascular collapse and ECG alterations typical of myocardial ischaemia. All these effects persisted throughout the ADP infusion but disappeared soon after its termination. They were almost completely inhibited in rats given SH 869 or made thrombocytopenic.

In conclusion, platelets seem to contribute to the cardiovascular effects of ADP only in certain experimental conditions. In others, the nucleotide’s direct effects seem more important.

• References

• 1 Angelakos ET, Glassman PM. 1965; Hypotensive and cardiac effects of adenosine and its phosphorylated derivatives. Archives Internationales de Pharmacodynamie et de Therapie 154: 82
• 2 Ashida SI, Abiko Y. 1975; Protective effect of pantethine on experimental thrombocytopenia in the rat. Thrombosis et Diathesis Haemorrhagica 33: 528
• 3 Born GVR. 1962; Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature (London) 194: 927
• 4 Didisheim P. 1972. Animal models useful in the study of thrombosis and antithrombotic agents. In: Spaet TH. (ed.) Progress in Hemostasis and Thrombosis. Grune & Stratton; New York: 165
• 5 Drury AN, Szent-Györgyi A. 1929; The physiological activity of adenine compounds with special reference to their action upon the mammalian heart. Journal of Physiology (London) 68: 213
• 6 Evensen SA, Jeremic M, Hjort PF. 1968; Experimental thrombocytopenia induced by Busulphan (Myleran) in rabbits: Extremely low platelet levels and intact plasma clotting system. Thrombosis et Diathesis Haemorrhagica 19: 570
• 7 Frohlich ED. 1963; Local effect of adenosine mono-di-, and triphosphate on vessel resistance. American Journal of Physiology 204: 28
• 8 Gordon DB. 1961; Basis of the depressor action of adenosine phosphates. American Journal of Physiology 201: 1126
• 9 Gordon DB, Hesse DH. 1961; Blood pressure lowering action of adenosine diphosphate and related compounds. American Journal of Physiology 201: 1123
• 10 Green HN, Stoner HB. 1950. Biological Actions of the Adenine Nucleotides. H. K. Lewis & Co.; London:
• 11 Holmsen H, Day HJ, Stormorken H. 1969. The blood platelet release reaction. Scandinavian Journal of Haematology. Suppl 8
• 12 Hyman AL, Woolverton WC, Pennington DG, Jaques WE. 1971; Pulmonary vascular responses to adenosine diphosphate. Journal of Pharmacology and Experimental Therapeutics 178: 549
• 13 James TN. 1965; The chronotropic action of ATP and related compounds studied by direct perfusion of the sinus node. Journal of Pharmacology and Experimental Therapeutics 149: 233
• 14 Jørgensen L, Rowsell HC, Hovig T, Glynn MF, Mustard JF. 1967; Adenosine diphosphate-induced platelet aggregation and myocardial infarction in swine. Laboratory Investigation 17: 616
• 15 Kobayashi I, Didisheim P. 1973; Systemic effects of ADP-induced platelet aggregation and their modification by aspirin and by pyridinolcarbamate. Thrombosis et Diathesis Haemorrhagica 30: 178
• 16 Massion WH. 1966; The role of reflex hypotension in pulmonary embolism. Pfluegers Archiv European Journal of Physiology (Basel) 288: 109
• 17 Moschos CB, Lahiri K, Peter A, Jesrani MU, Regan TJ. 1972; Effect of aspirin upon experimental coronary and non-coronary thrombosis and arrhythmia. American Heart Journal 84: 525
• 18 Nordöy A, Chandler AB. 1964; Platelet thrombosis induced by adenosine diphosphate in the rat. Scandinavian Journal of Haematology 1: 16
• 19 Olsson P, Rådegran K, Taylor GA. 1970; Haemodynamic changes resulting from thrombin induced intravascular coagulation. Cardiovascular Research 4: 443
• 20 Rådegran K. 1972; The effect of acetylsalicyclic acid and the peripheral and pulmonary vascular responses to thrombin. Acta Anaesthesiologica Scandinavica 16: 140
• 21 Rådegran K, Bergentz SE, Lewis DH, Ljungqvist U, Olsson P. 1971; Pulmonary effects of induced platelet aggregation. Intravascular obstruction or vasoconstriction? Scandinavian Journal of Clinical and Laboratory Investigation 28: 423
• 22 Reeves JT, Jokl P, Merida J, Leathers JE. 1967; Pulmonary vascular obstruction following administration of high-energy nucleotides. Journal of Applied Physiology 22: 475
• 23 Reyers-Degli Innocenti I, Poggi A, De Gaetano G. 1974; Platelet aggregation and haemolysis induced in rats by intravenous infusion of ADP. Effect of potentially antithrombotic drugs. Scandinavian Journal of Haematology 13: 331
• 24 Stafford A. 1966; Potentiation of adenosine and the adenine nucleotides by dipyridamole. British Journal of Pharmacology and Chemotherapy 28: 218
• 25 Urthaler F, James TN. 1972; Effects of adenosine and ATP on AV conduction and on AV junctional rhythm. Journal of Laboratory and Clinical Medicine 79: 96