Effects Of Aspirin And Sulfinpyrazone On Platelets, Vascular Cells And Their Interactions

Abstract

Sulfinpyrazone (SUL) and aspirin (ASA) are potentially useful antithrombotic drugs. Both drugs are thought to exert this effect by inhibiting the platelet enzyme, cyclooxygenase (C-0), thus preventing thromboxane A2 synthesis. Recent data, however, suggest that these drugs also may affect vessel wall cells. To study this further, we examined the effects of SUL and ASA on i) the adhesion of 3H-adenine-labelled washed human platelets to cultured bovine endothelial (EC) and smooth muscle cells (SMC), ii) EC and SMC DNA synthesis (3H-thymidine incorporation) and iii) cell growth. Pretreatment of platelets with 100μM ASA or 250μM SUL (concentrations sufficient to inhibit C-0), did not affect platelet adhesion to untreated EC or SMC. However, adhesion of untreated, ASA- and SUL-platelets was increased 25,28 and 44% resp. when EC were pretreated with 650μM SUL for 24 hr. In contrast, adhesion of ASA-platelets to EC pretreated with lOOμM ASA (sufficient to inhibit prostacyclin), was unaffected. Platelet adhesion to SMC pretreated with 650μM SUL for 24 hr was decreased when platelets also were pretreated with ASA (20%, p<0.05) or SUL (27%, pc 0.02). Pretreatment of SMC with SUL for only 2 hr had no effect. DNA synthesis in EC and SMC treated with 62.5 and 250μM SUL for 24 hr, was inhibited >35% and >95% resp. Preliminary data suggest that this inhibitory effect may last longer in SMC. To study the effect of SUL on cell growth, EC and SMC were plated at 2 × 104 cells/ cm2 and fed with culture medium containing 0, 62.5 or 625uM SUL on day 0, 1, 3 and 4.5. EC growth rate and final density were unaffected over 7 days. SMC growth rate also was unaffected, but the final density of SMC treated with 650μM SUL was 31 μ 2% less than untreated SMC at 7 days (p<0.01). These data indicate that SUL has direct effects on EC and SMC that may influence i) platelet-vessel wall interactions and ii) vascular cell proliferation.