title: Trimethylamine-N-oxide: a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats.
abstract: BACKGROUND
  Recent evidence suggests that an elevated plasma trimethylamine N-oxide (TMAO) level is associated with an increased risk of adverse cardiovascular events in humans; however, the mechanism is not clear. The aims of this study were to establish the plasma TMAO level in rats and to evaluate the effect of TMAO on arterial blood pressure (BP) and the hemodynamic effects of angiotensin II (Ang II).
  
  
  METHODS
  Twelve-week-old, Sprague-Dawley rats were implanted with telemetric transmitters, and continuous recordings of heart rate, systolic BP (SBP), and diastolic BP (DBP) were made for 7 days before and 14 days during osmotic minipump-driven subcutaneous infusion of saline (controls), TMAO, low-dose Ang II, or Ang II + TMAO. Plasma TMAO concentration was evaluated using liquid chromatography coupled with triple-quadrupole mass spectrometry.
  
  
  RESULTS
  The plasma TMAO concentration in controls was 0.57 μmol/L, whereas in TMAO-infused rats it was 58 μmol/L. Neither saline nor TMAO infusion affected SBP and DBP. Infusion of Ang II significantly increased SBP and DBP for the first 5 days of infusion only. In contrast, infusion of Ang II + TMAO produced a hypertensive response that lasted until the end of the experiment. TMAO infusions did not affect body weight and motor activity.
  
  
  CONCLUSIONS
  We showed that physiological plasma TMAO concentration in rats was approximately 10 times lower than that reported in humans. Furthermore, the new finding of the study is that TMAO does not affect BP in normotensive animals. However, it prolongs the hypertensive effect of Ang II.
authors.affiliation: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland. Electronic address: mufnal@wum.edu.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Ufnal
authors.affiliation: Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Jazwiec
authors.affiliation: Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Dadlez
authors.affiliation: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Drapala
authors.affiliation: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Sikora
authors.affiliation: Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Skrzypecki
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008744:Methylamines / Q000493:pharmacokinetics*; D016877:Oxidants / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008744:Methylamines; D016877:Oxidants; D000804:Angiotensin II; C005855:trimethyloxamine