Increased circulating trimethylamine N-oxide plays a contributory role in the development of endothelial dysfunction and hypertension in the RUPP rat model of preeclampsia

OBJECTIVE: We examined whether trimethylamine-N-oxide (TMAO) plays a role in endothelial dysfunction and hypertension in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia (PE). Methods: Normal pregnant rats and RUPP rats were treated without or with 3,3-Dimethyl-1-butanol (DMB, a TMAO inhibitor) from gestational day 14. Results: On day 19 of gestation, RUPP rats had higher plasma TMAO, impaired vasodilation and hypertension, decreased interleukin (IL)-10, increased superoxide production and proinflammatory cytokines in the aorta. All of which were reversed by DMD. Conclusion: Increased circulating TMAO downregulates IL-10 and promotes vascular inflammation and oxidative stress, contributing to endothelial dysfunction and hypertension in PE.