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Deep-water animals accumulate TMAO to protect proteins, such as lactate dehydrogenase (LDH), against hydrostatic pressure stress (HPS). We hypothesized that TMAO exerts beneficial effects on the circulatory system and protects cardiac LDH exposed to HPS produced by the contracting heart. Male, Sprague-Dawley and Spontaneously-Hypertensive-Heart-Failure (SHHF) rats were treated orally with either water (control) or TMAO. In vitro, LDH with or without TMAO was exposed to HPS and was evaluated using fluorescence correlation spectroscopy. TMAO-treated rats showed higher diuresis and natriuresis, lower arterial pressure and plasma NT-proBNP. Survival in SHHF-control was 66% vs 100% in SHHF-TMAO. In vitro, exposure of LDH to HPS with or without TMAO did not affect protein structure. In conclusion, TMAO reduced mortality in SHHF, which was associated with diuretic, natriuretic and hypotensive effects. HPS and TMAO did not affect LDH protein structure.<\/jats:p>","DOI":"10.7554\/elife.57028","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T08:00:27Z","timestamp":1591603227000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.57028","source":"Crossref","is-referenced-by-count":53,"title":["TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats"],"prefix":"10.7554","volume":"9","author":[{"given":"Marta","family":"Gawrys-Kopczynska","sequence":"first","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Konop","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Maksymiuk","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Kraszewska","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladislav","family":"Derzsi","sequence":"additional","affiliation":[{"name":"Department of Soft Condensed Matter, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Sozanski","sequence":"additional","affiliation":[{"name":"Department of Soft Condensed Matter, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Holyst","sequence":"additional","affiliation":[{"name":"Department of Soft Condensed Matter, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Pilz","sequence":"additional","affiliation":[{"name":"Department of Soft Condensed Matter, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Samborowska","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leszek","family":"Dobrowolski","sequence":"additional","affiliation":[{"name":"Department of Renal and Body Fluid Physiology, M. 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