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 levels3,4. 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-PGF1α) 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.
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Affiliations
Department of Surgery, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215
- Michael L. Steer
- , D. Euan MacIntyre
- & Edwin W. Salzman
Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02154
- L. Levine
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