Platelet interaction with vascular smooth muscle in synthesis of prostacyclin

Because vascular smooth muscle cells (SMC) can be exposed to platelets at sites of significant arterial injury, we studied whether cultured rat aorta SMC can utilize platelet-derived arachidonate and prostaglandin (PG) endoperoxides (PGG₂/PGH₂) in the synthesis of prostacyclin (PGI₂). SMC converted exogenous PGH₂ to PGI₂, measured by radioimmunoassay (RIA) of 6-keto-PGF(1α), despite cyclooxygenase inhibition or PGH₂-receptor blockade. SMC produced increasing amounts of PGI₂ in the presence of an increasing number of platelets when the two cell types were coincubated with arachidonate. Furthermore, aspirin-pretreated SMC produced PGI₂ in response to arachidonate, ionophore A23187, or thrombin in the presence of platelets but not in their absence. SMC, by themselves unresponsive to thrombin, produced PGI₂ during coincubation with thrombin-stimulated aspirin-pretreated platelets. Separation of the SMC monolayer and platelets with a filter did not prevent platelet-dependent PGI₂ formation by the SMC. Finally, aspirin-pretreated SMC, in cosuspension with platelets, inhibited platelet aggregation in association with PGI₂ production. These data indicate that 1) SMC can synthesize PGI₂ from exogenously added PGH₂ and from platelet-derived arachidonate or endoperoxides, 2) direct cell-cell contact is not required for intercellular endoperoxide transfer, and 3) SMC can inhibit platelet aggregation possibly through PGI₂ production from platelet-derived endoperoxides.