Thromboxane A 2 Regulates Vascular Tone via Its Inhibitory Effect on the Expression of Inducible Nitric Oxide Synthase
- 11 November 2003
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation
- Vol. 108 (19) , 2381-2386
- https://doi.org/10.1161/01.cir.0000093194.21109.ec
Abstract
Background— Circulatory failure in sepsis arises from vascular hyporesponsiveness, in which nitric oxide (NO) derived from inducible NO synthase (iNOS) plays a major role. Details of the cross talk between thromboxane (TX) A2 and the iNOS–NO system, however, remain unknown. We intended to clarify the role of TXA2, via the cross talk, in vascular hyporesponsiveness. Methods and Results— We examined cytokine-induced iNOS expression and NO production in cultured vascular smooth muscle cells (VSMCs) and cytokine-induced hyporesponsiveness of the aorta from mice lacking the TXA2 receptor (TP−/− mice). The cytokine-induced iNOS expression and NO production observed in wild-type VSMCs were significantly augmented in TP−/− VSMCs, indicating an inhibitory effect of endogenous TXA2 on iNOS expression. Furthermore, in indomethacin-treated wild-type VSMCs, U-46619, a TP agonist, inhibited cytokine-induced iNOS expression and NO production in a concentration-dependent manner, effects absent from TP−/− VSMCs. In an ex ...Keywords
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