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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...

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Published in:Canadian journal of cardiology 2014-12, Vol.30 (12), p.1700-1705
Main Authors: Ufnal, Marcin, PhD, MD, Jazwiec, Radoslaw, MSc, Dadlez, Michal, PhD, Drapala, Adrian, MD, Sikora, Mariusz, MD, Skrzypecki, Janusz, MD
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cited_by cdi_FETCH-LOGICAL-c411t-826941cf3cf2cc65afbd589109750065fc57c180822a49812cc9a53fbc527f3
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container_end_page 1705
container_issue 12
container_start_page 1700
container_title Canadian journal of cardiology
container_volume 30
creator Ufnal, Marcin, PhD, MD
Jazwiec, Radoslaw, MSc
Dadlez, Michal, PhD
Drapala, Adrian, MD
Sikora, Mariusz, MD
Skrzypecki, Janusz, MD
description 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.
doi_str_mv 10.1016/j.cjca.2014.09.010
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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.</description><identifier>ISSN: 0828-282X</identifier><identifier>EISSN: 1916-7075</identifier><identifier>DOI: 10.1016/j.cjca.2014.09.010</identifier><identifier>PMID: 25475471</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Angiotensin II - adverse effects ; Animals ; Blood Pressure - drug effects ; Cardiovascular ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Hypertension - metabolism ; Hypertension - physiopathology ; Male ; Methylamines - pharmacokinetics ; Oxidants - pharmacology ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Canadian journal of cardiology, 2014-12, Vol.30 (12), p.1700-1705</ispartof><rights>Canadian Cardiovascular Society</rights><rights>2014 Canadian Cardiovascular Society</rights><rights>Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. 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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. 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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.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>25475471</pmid><doi>10.1016/j.cjca.2014.09.010</doi><tpages>6</tpages></addata></record>
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subjects Angiotensin II - adverse effects
Animals
Blood Pressure - drug effects
Cardiovascular
Chromatography, High Pressure Liquid
Disease Models, Animal
Hypertension - metabolism
Hypertension - physiopathology
Male
Methylamines - pharmacokinetics
Oxidants - pharmacology
Rats
Rats, Sprague-Dawley
title Trimethylamine-N-Oxide: A Carnitine-Derived Metabolite That Prolongs the Hypertensive Effect of Angiotensin II in Rats
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