Differential action of spasmolytic vasodilators on platelet aggregation and endothelial cell-dependent...

The perioperative use of spasmolytic vasodilators during reconstructive or vascular surgery is an important therapeutic procedure to prevent vascular spasm. Platelet aggregation at vascular endothelium injured by the surgical manipulation is thought to be associated with the persistency of spasm, although little is known about the effects of these drugs on platelet aggregation and on anti-aggregation provoked by endothelial cells.

(1) To test the direct effect of vasodilators against platelet aggregation, change in light transmission through platelet-rich plasma (PRP) stimulated with 4 microg/ml collagen was measured in the absence or presence of pentobarbital, papaverine, prostaglandin E1 (PGE1), trinitroglycerin, nitroprusside, nicardipine, and diltiazem. (2) Effects of these drugs on endothelial cell-dependent anti-aggregation were then evaluated. Incubation buffer of cultured porcine aortic endothelial (PAE) cells, which were preincubated with vasodilators for 10 min prior to a 1-min stimulation with 1 microM bradykinin, was transferred to collagen-stimulated PRP.

(1) Papaverine and PGE1 directly inhibited platelet aggregation in a concentration-dependent manner. All other drugs failed to inhibit aggregation. (2) Incubation buffer of PAE cells stimulated with bradykinin showed a potent anti-aggregation. Pentobarbital concentration-dependently inhibited the endothelial cell-dependent anti-aggregation. Every other drug did not inhibit the anti-aggregation by PAE cells.

Because of the direct anti-aggregatory effect without inhibiting endothelial cell-dependent anti-aggregation, we suggested that papaverine and PGE1 were the most promising vasodilators of all drugs examined in this study while further evaluation is required for the clinical relevance of the present study.