The facilitating effects of adrenaline on platelet aggregation

Abstract

Adrenaline induced platelet aggregation has been shown by others to depend largely on the cyclooxygenase pathway of arachidonate metabolism. Acetylsalicylic acid, an inhibitor of the enzyme cyclooxygenase, does not prevent, however, the ability of adrenaline to potentiate aggregation caused by other agonists. Thromboxane B 2 (T×B 2) production associated with adrenaline potentiation of ADP and arachidonate-induced platelet aggregation was determined with and without various cyclooxygenase inhibitors, to further investigate the involvement of the enzyme cyclooxygenase in adrenaline potentiation of responses caused by other agents. It was shown that adrenaline stimulated a cyclooxygenase independent pathway resulting in potentiation of platelet aggregation. Contrary to other reports, adrenaline also stimulated the cyclooxygenase pathway to an extent sufficient to generate T×B 2 when platelets were under the inhibitory influence of acetylsalicylic acid. Lower concentrations of indomethacin, and BW755C, a dual cyclooxygenase and lipoxygenase inhibitor, did not enable adrenaline to potentiate arachidonate-induced aggregation, but did allow adrenaline potentiation of ADP-induced aggregation. There must therefore be at least two mechanisms by which adrenaline can potentiate platelet aggregation. These observations may have implications for the management by aspirin of some patients with cardiovascular diseases. For example, “stressed” subjects with elevated catecholamines may fail to respond to therapy for reasons outlined above.