The obligatory role of host microbiota in bioactivation of dietary nitrate.

Autor: Moretti C; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden. Electronic address: chiara.moretti@ki.se., Zhuge Z; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden., Zhang G; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden; Department of Neurobiology, Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China., Haworth SM; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden., Paulo LL; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden; Biotechnology Center, Federal University of Paraiba, Joao Pessoa, PB, Brazil., Guimarães DD; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden., Cruz JC; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden; Biotechnology Center, Federal University of Paraiba, Joao Pessoa, PB, Brazil., Montenegro MF; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden., Cordero-Herrera I; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden., Braga VA; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden; Biotechnology Center, Federal University of Paraiba, Joao Pessoa, PB, Brazil., Weitzberg E; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden., Carlström M; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden., Lundberg JO; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden. Electronic address: jon.lundberg@ki.se.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2019 Dec; Vol. 145, pp. 342-348. Date of Electronic Publication: 2019 Oct 07.
DOI: 10.1016/j.freeradbiomed.2019.10.003
Abstrakt: Nitric oxide (NO) is a key signalling molecule in the regulation of cardiometabolic function and impaired bioactivity is considered to play an important role in the onset and progression of cardiovascular and metabolic disease. Research has revealed an alternative NO-generating pathway, independent of NO synthase (NOS), in which the inorganic anions nitrate (NO 3 - ) and nitrite (NO 2 - ) are serially reduced to form NO. This work specifically aimed at investigating the role of commensal bacteria in bioactivation of dietary nitrate and its protective effects in a model of cardiovascular and metabolic disease. In a two-hit model, germ-free and conventional male mice were fed a western diet and the NOS inhibitor l-NAME in combination with sodium nitrate (NaNO 3 ) or placebo (NaCl) in the drinking water. Cardiometabolic parameters including blood pressure, glucose tolerance and body composition were measured after six weeks treatment. Mice in both placebo groups showed increased body weight and fat mass, reduced lean mass, impaired glucose tolerance and elevated blood pressure. In conventional mice, nitrate treatment partly prevented the cardiometabolic disturbances induced by a western diet and l-NAME. In contrast, in germ-free mice nitrate had no such beneficial effects. In separate cardiovascular experiments, using conventional and germ-free animals, we assessed NO-like signalling downstream of nitrate by administration of sodium nitrite (NaNO 2 ) via gavage. In this acute experimental setting, nitrite lowered blood pressure to a similar degree in both groups. Likewise, isolated vessels from germ-free mice robustly dilated in response to the NO donor sodium nitroprusside. In conclusion, our findings demonstrate the obligatory role of host-microbiota in bioactivation of dietary nitrate, thus contributing to its favourable cardiometabolic effects.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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