TMAO, a carnitine-derived metabolite, prolongs the hypertensive effect of Ang 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 plasma TMAO level in rats as well as to evaluate the effect of TMAO on arterial blood pressure (BP) and hemodynamic effects of angiotensin II (Ang II). Methods 12-week-old, Sprague-Dawley rats were implanted with telemetry transmitters and continuous recordings of heart rate, systolic (SBP) and diastolic (DBP) arterial blood pressures were made for 7 days before and 14 days during osmotic minipump-driven subcutaneous infusion of either: 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 Plasma TMAO concentration in controls was 0.57 μmol/L, while 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 hypertensive response which 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 ten 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.