Effects of the coumarin derivative AD6 on platelet aggregation, platelet vessel wall interactions and 6 keto PGF1 alpha production in perfused aortas, in experimentally hypercholesterolaemic rabbits

The coumarin derivative AD6 was administered i.v. at the dose of 3 mg/kg/day to hypercholesterolaemic rabbits for a period of three weeks, while continuing the hypercholesterolaemic treatment (HC + AD6). A second group of hypercholesterolaemic (HC) rabbits was injected with saline and a third group of animals was composed of normal rabbits (N). Platelet aggregatory responses to arachidonic acid (AA) and collagen, thromboxane B2 (TxB2) formation after stimulation with collagen, 6 keto PGF1α formation following perfusion of isolated aortas with platelet-rich plasmas (PRP) and sensitivity of PRP to the inhibitory activity of exogenous prostacyclin (PGI2) were studied. Platelets of the HC rabbits were hyperactive to AA, were less sensitive to PGI2, produced less TxB2 after collagen stimulation, and perfused aortas of the same HC group produced more 6 keto PGF1α in respect to the N animals. Administration of AD6 to the HC animals normalized TxB2 production in stimulated PRP, platelet sensitivity to PGI2 and 6 keto PGF1α production in perfused aortas.