Is prostacyclin a physiologically important circulating anti-platelet agent?

Prostacyclin (PGI 2 ) is a naturally occurring arachidonic acid metabolite which causes relaxation of vascular smooth muscle 1 and is the most potent inhibitor of platelet aggregation known 2 . The anti-aggregatory effects of PGI 2 result from its ability to stimulate platelet adenylate cyclase and elevate platelet cyclic AMP levels 3,4 . The possibility that PGI 2 is a circulating hormone that acts to inhibit platelet aggregation in vivo was first suggested by Gryglewski et al. 5 and Moncada et al. 6 . In their studies using heparinised rabbits and cats, exogenous PGI 2 caused a decrease in superfused ex vivo tendon weight, and this effect was inhibited by infusion of antiserum directed against a stable PGI 2 analogue (5,6-dihydro-PGI 2 ). Tendon weight gain occurred in the absence of exogenous PGI 2 and was enhanced by infusion of PGI 2 -binding antibodies, an effect that was more pronounced in arterial than in venous blood. In contrast, Smith and coworkers 7 observed that their PGI 2 -binding antibodies (antiserum directed against 6-keto-PGF 1 α ) suppressed the vasodepressor effects of exogenous PGI 2 infused into cats but did not alter blood pressure in the absence of exogenous PGI 2 . They concluded that PGI 2 is not a circulating vasodepressor hormone. The present studies were designed to examine the physiological role, if any, of circulating PGI 2 in the regulation of human platelet function. Here, we report the results of experiments dealing with the effects of PGI 2 and antibodies directed against 5,6-dihydro-PGI 2 on human platelet function and cyclic AMP levels. These studies indicate that, in humans, PGI 2 is not a physiologically important circulating inhibitor of platelet aggregation.