The modification of platelet-induced coronary vasoconstriction by a thromboxane receptor antagonist.
The role of platelet-derived vasoconstrictors in coronary vasospasm was studied using arachidonic acid-stimulated washed human platelets (WPS). Transfer of this system into an organ bath, containing bovine coronary arteries (BCA) and a mixture of blocking agents resulted in a biphasic contraction, consisting of a first phase, mediated by release of thromboxane (TX) A2 and a second phase, mediated by release of 5-hydroxytryptamine (5-HT) from the WPS (1,2). Treatment of the WPS with 4-[2-(benzenesulfonamido)-ethyl]-phenoxyacetic acid (BM 13.177) (0.03-3 mumol/L) prior to stimulation revealed a concentration-dependent inhibition of the 5-HT component of the contractile response with a minor reduction of the TXA2 component of contraction and enhanced amounts of immunoreactive TXB2 in the bath fluid. Treatment of the BCA with BM 13.177 prior to addition of stimulated WPS resulted in a significant reduction of the TXA2 component of contraction, by 56% at 30 mumol/L whereas 3 mumol/L were ineffective. The 5-HT component of contraction was enhanced. For comparison, the IC50 for BM 13.177 to inhibit PGF2 alpha-induced contractions was 6 mumol/L and that to inhibit U-46,619 was 0.5 mumol/L. BM 13.177 was at least 1 order of magnitude more potent as an inhibitor of U-46,619 than of PGF2 alpha- or TXA2-induced contractions. It is concluded that BM 13.177 is a weak inhibitor of TXA2-mediated contractions of coronary vessels, suggesting different thromboxane receptors in coronary vessels and platelets.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D012701:Serotonin / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D001095:Arachidonic Acids; D013449:Sulfonamides; D016718:Arachidonic Acid; D012701:Serotonin; D013928:Thromboxane A2; C040624:sulotroban; D000242:Cyclic AMP