Investigation of the effect of thromboxane receptor on control of vascular tone in coronary artery bypass graft materials

Aspirin, the antithrombotic drug used after the coronary artery bypass operation, inhibits thromboxane (TxA2) synthesis and increases the patency rate of bypass graft materials such as saphenous vein (SV) and internal mammary artery (IMA). However, aspirin resistance is observed in some patients after bypass operation. Therefore, novel treatment approaches that specifically inhibit TxA2 effect is necessary. We aimed to investigate the effect of TxA2 pathway in the control of vascular tone in SV and IMA. Using an organ bath system, vascular reactivity induced by different spasmogens; [prostaglandin (PG)E2, PGF2α, U46619, phenylephrine or arachidonic acid (AA)] were tested in SV and IMA preparations in the presence of: TP receptor antagonist (BAY u3405), aspirin and TxA2 synthase inhibitor (furegrelate). In order to evaluate whether there is a shift towards other prostanoids in the presence of furegrelate, IP receptor antagonist (CAY10441) and/or PGE2 (EP4) receptor antagonist (GW627368X) were used. Our results demonstrate that BAY u3405 significantly inhibits the contraction responses induced by PGE2, PGF2α, U46619 and AA in IMA and SV. Aspirin significantly increases the contraction responses induced by phenylephrine in IMA and reduces the contraction response induced by AA in SV. Furegrelate significantly reduces the contraction responses induced by PGE2 and AA in both grafts. The reduced contraction induced by PGE2 in the presence of furegrelate is reversed by CAY10441 with/without GW627368X. We suggest that BAY u3405 or furegrelate could be used as an alternative to aspirin after bypass operation and contribute to the prevention of spasm that occurs after bypass operation.