Ibuprofen or ozagrel increases NO release and l-nitro arginine induces TXA2 release from cultured porcine basilar arterial endothelial cells

The vascular resting tone of the porcine basilar artery appears to be mostly maintained by a balance between spontaneously released nitric oxide (NO) from endothelial cells and thromboxane (TX) A2 from endothelial and smooth muscle cells. However the precise role of the interaction between the above two substances in the control of vascular tone is unclear. We attempted to clarify the interaction between NO and TXA2 using cultured porcine basilar arterial endothelial cells. The cultured endothelial cells produced NO spontaneously, while TXB2 (a stable metabolite of TXA2) production remained below the detection limit. Ibuprofen (a COX inhibitor) and ozagrel (a TXA2 synthetase inhibitor) significantly increased the spontaneous production of NO, which was not affected by 1400W (an iNOS inhibitor). l-Nitro arginine (a NOS inhibitor) significantly induced TXB2 production. These results suggest that NO may inhibit COX or TXA2 synthetase, and that therefore inhibition of NOS might disinhibit COX or TXA2 synthetase, subsequently inducing TXA2 production. On the other hand, as TXA2 and other contractility-related prostaglandin(s) may inhibit NOS, therefore the inhibition of COX or TXA2 synthetase might disinhibit NOS, and then increase the spontaneous production of NO in porcine basilar arterial endothelial cells.