Beneficial Effect of TMAO in Spontaneously Hypertensive Heart Failure Rats is Associated with Diuretic and Hypotensive Actions.

There is an ongoing debate weather trimethylamine‐oxide (TMAO), a molecule present in seafood and a derivate of microbiota metabolism, is beneficial or harmful for the circulatory system. Numerous biophysical studies show that TMAO protects proteins exposed to osmotic and hydrostatic stress (HS). We hypothesized that TMAO may benefit the circulatory system by protecting cardiac proteins exposed to HS produced by the contracting heart. Male, 6‐week‐old, Sprague‐Dawley (SD, n=40) and Spontaneously‐Hypertensive‐Heart‐Failure (SHHF, n=18) rats were randomly divided into either control (Water) or TMAO treatment. After 50 weeks, half of SD were given Isoprenaline (s.c.) to increase arterial blood pressure (BP) and produce a mild, Takotsubo‐like cardiomyopathy (ISO). In vitro, cardiac lactic dehydrogenase (LDH) with or without TMAO was exposed to HS (changes in hydrostatic pressure similar, and higher than those present in the heart) for up to 24hrs and was evaluated using fluorescence correlation spectroscopy. After 58 weeks of the treatment survival was 100% in SD‐Water, SD‐TMAO, ISO‐TMAO and 90% in ISO‐WATER. In SHHF‐Water survival was 66% vs 100% in SHHF‐TMAO (p=0.065). In general, TMAO‐treated rats showed higher natriuresis and diuresis. In comparison to SHHF‐Water, SHHF‐TMAO showed significantly lower plasma NT‐proBNP, lower diastolic BP, lower liver angiotensinogen expression and a trend towards lower cardiac fibrosis. In vitro, exposure of LDH to HS with or without TMAO did not affect the protein structure. TMAO does not exert negative effects. In contrast, TMAO reduces mortality in HF rats that is associated with natriuretic, diuretic and hypotensive effects. HS produced by the contracting heart is neutral for cardiac LDH protein structure. Support or Funding Information Supported by National Science Centre, Poland grant no 2018/31/B/NZ5/00038.