an-vivo-method-for-evaluating-gut-blood-barrier-liver-metabolism

An <em>In Vivo</em> Method for Evaluating the Gut-Blood Barrier and Liver Metabolism of Microbiota Products

The gut-blood barrier (GBB) controls the passage of nutrients, bacterial metabolites and drugs from intestinal lumen to the bloodstream. The GBB integrity ...

Medical University of Warsaw

Several studies suggest negative effects of trimethylamine oxide (TMAO) on the circulatory system. However, a number of studies showed protective functions of TMAO, a piezolyte and osmolyte, in animals exposed to high hydrostatic and/or osmotic stress. We evaluated the effects of TMAO treatment on the development of hypertension and its complications in male, Spontaneously Hypertensive Rats maintained on water (SHR-WATER) and SHR drinking TMAO water solution from weaning (SHR-TMAO). Wistar-Kyoto rats (WKY) were used as normotensive controls to discriminate between age-dependent and hypertension-dependent changes. Telemetry measurements of blood pressure (BP) were performed in rats between 7 and 16 week of life. Anaesthetized rats underwent echocardiographic, electrocardiographic and direct left ventricular end-diastolic pressure (LVEDP) measurements. HE and van Gieson staining for histopathological evaluation were performed. Plasma TMAO measured by chromatography coupled with mass spectrometry was significantly higher in SHR-WATER than in WKY (≈20%). TMAO treatment increased plasma TMAO by 4-5-fold, and did not affect the development of hypertension in SHR. 16-week-old SHR-WATER and SHR-TMAO (12-week-TMAO-treatment) showed similar BP, angiopathy and cardiac hypertrophy. However, SHR-TMAO had lower plasma NT-proBNP, LVEDP, and cardiac fibrosis. In contrast to age-matched WKY, 60-week-old SHR showed hypertensive angiopathy and heart failure with preserved ejection fraction. In comparison to SHR-WATER, SHR-TMAO (56-week-TMAO-treatment) showed significantly lower plasma NT-proBNP and vasopressin, significantly lower LVEDP and cardiac fibrosis. In conclusion, 4-5-fold increase in plasma TMAO does not exert negative effects on the circulatory system. In contrast, increased dietary TMAO seems to reduce diastolic dysfunction in pressure-overloaded heart in rats.

Marta Gawrys

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