TMAO affects hemodynamic response to Ang II and restraint stress in rats

Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCA018

Poster Communications: TMAO affects hemodynamic response to Ang II and restraint stress in rats

M. Ufnal1, R. Jazwiec2, A. Drapala1, M. Sikora1, S. Janusz1, M. Dadlez2

1. Department of Experimental and Clinical Physiology, The Medical University of Warsaw, Warsaw, Poland. 2. Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.

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Trimethylamine N-oxide (TMAO) is the organic compound which concentration in the blood increases after ingestion of dietary phosphatidylcholine. Major sources of phosphatidylcholine include red meat. Resent evidence suggest that elevated fasting plasma levels of TMAO is associated with increased risk of major adverse cardiovascular events in humans (1). There is no data available on the effects of TMAO on arterial blood pressure (BP), and plasma TMAO level in rats has not been established. We checked the plasma level of TAMO in rats as well as the effect of TMAO on BP at baseline and during restraint stress in normotensive rats and rats with angiotensin II (Ang II)-induced hypertension.We did the study on four groups (n=6) of male, Sprague Dawley rats weighing 300-320g, fed standard laboratory chow. The experiments were made according to the Directive 2010/63/EU and approved by the Ethical Committee of the Medical University of Warsaw. Rats were implanted with telemetric transmitters (DSI) and continuous recordings of BP and animal activity were made for 7 days before and 28 days during osmotic minipump driven subcutaneous infusion of either: saline, TMAO (0.65 mg/hr), angiotensin II (Ang II, 2.96 µg/hr) or Ang II + TMAO. After two weeks of infusions rats were subjected to one hour restraint stress induced by immobilization of rats in plastic tubes. This was repeated for the following 3 days. After the experiments plasma was collected for evaluation of TMAO concentration using liquid chromatography coupled with triple-quadrupole mass spectrometry. All surgical procedures were performed under general anaesthesia with ketamine 30mg and xylazine 3mg IP.Neither infusion of saline or TMAO affected mean arterial blood pressure (MABP). Infusion of Ang II significantly increased MABP. In contrast, combined infusion of Ang II and TMAO failed to affect MABP. Restraint stress significantly increased MABP in all the groups, however rats treated with Ang II and Ang II + TMAO showed higher increase in MABP than groups treated with saline or TMAO alone. Baseline plasma concentration of TMAO in rats was 36.3 ng/mL ± 2.8 (means±SE), which is about 10 times lower than that reported in humans (1). Chronic infusion of TMAO increased its plasma concentration to 4.6 µg/mL ± 0.4, with no effect on well-being and motor activity of rats.In conclusion, plasma levels of TAMO are lower in rats than in humans, which likely results from differences in a diet. This study suggests that TMAO affects BP, however the effects are ambiguous and may depend on the presence of Ang II or stress hormones. As this is the first study on the hemodynamic effects of TMAO in mammals further research is needed to clarify its hemodynamic effects and possible involvement in cardiovascular diseases such as hypertension.



Where applicable, experiments conform with Society ethical requirements.

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