IMPAIRED RESPONSIVENESS OF PLATELETS FROM PATIENTS WITH STABLE ANGINA-PECTORIS TO ANTIAGGREGATING AND CYCLICAMP-ELEVATING EFFECTS OF PROSTAGLANDIN E(1)

The antiplatelet effects of prostacyclin (PGI(2)) and prostaglandin E( 1) (PGE(1)) are mediated by the same receptor and are secondary to int raplatelet cyclicAMP formation. Therefore, any dysfunction in PGI(2)/P GE(1)-stimulated stimulated cyclicAMP generation might lead to patholo gically increased platelet aggregation. This possible consequence has not yet been studied. We examined antiaggregating effects of PGE(1) in comparison with its cyclicAMP-elevating potency in platelets obtained from normal subjects and patients with stable angina pectoris; platel et hyperaggregability in such patients has been documented by us previ ously. ADP-induced aggregation was measured in platelet-rich plasma (P RP); PGE(1) was added to platelets 0.5 min after ADP for assessment of reversal of incipient aggregation. Concentrations of PGE(1) associate d with 50% reversal of aggregation (C-50) were 2.4 +/- 0.3 x 10(-8) M in normal subjects and 6.3 +/- 1.6 x 10(-7) M in patients (p < 0.01). PGE(1) produced a concentration-dependent increase in intraplatelet cy clicAMP, and there was a strong correlation between cyclicAMP-stimulat ing and antiaggregating effects of PGE(1). Maximal increases in cyclic AMP with PGE(1) 10(-4) M were 330 +/- 10% for normal subjects and 220 +/- 20% for patients (p < 0.01). Thus, the observed decrease in PGE(1) -induced reversal of platelet aggregation in patients can be attribute d to a suppressed cyclicAMP response to PGE(1). These results are like ly also to imply reduced platelet sensitivity in vivo to endogenous PG E(1) and PGI(2), which in turn might contribute to platelet hyperaggre gability observed in cardiovascular diseases.