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 7th and 16th 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.