Is prostacyclin a physiologically important circulating anti-platelet agent?

Abstract

Prostacyclin (PGI₂) is a naturally occurring arachidonic acid metabolite which causes relaxation of vascular smooth muscle¹ and is the most potent inhibitor of platelet aggregation known². The anti-aggregatory effects of PGI₂ result from its ability to stimulate platelet adenylate cyclase and elevate platelet cyclic AMP levels^3,4. The possibility that PGI₂ 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 PGI₂ caused a decrease in superfused ex vivo tendon weight, and this effect was inhibited by infusion of antiserum directed against a stable PGI₂ analogue (5,6-dihydro-PGI₂). Tendon weight gain occurred in the absence of exogenous PGI₂ and was enhanced by infusion of PGI₂-binding antibodies, an effect that was more pronounced in arterial than in venous blood. In contrast, Smith and coworkers⁷ observed that their PGI₂-binding antibodies (antiserum directed against 6-keto-PGF_1α) suppressed the vasodepressor effects of exogenous PGI₂ infused into cats but did not alter blood pressure in the absence of exogenous PGI₂. They concluded that PGI₂ is not a circulating vasodepressor hormone. The present studies were designed to examine the physiological role, if any, of circulating PGI₂ in the regulation of human platelet function. Here, we report the results of experiments dealing with the effects of PGI₂ and antibodies directed against 5,6-dihydro-PGI₂ on human platelet function and cyclic AMP levels. These studies indicate that, in humans, PGI₂ is not a physiologically important circulating inhibitor of platelet aggregation.