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 aquimolar 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 effects seen more important.