LAUSR

Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite produced from choline and phosphatidylcholine and it has recently been related to risk for cardiovascular diseases. This study tests the hypothesis that TMAO would contribute to impaired endothelium dependent relaxation in db/db mice. Sixteen week old male lean and db/db mice were euthanized and the small mesenteric arteries (SMA) were mounted in a wire myograph. Concentration response curves to phenylephrine (PE; 1 nM- 30 μM) and acetylcholine (ACh; 1 nM- 30 μM) were performed in the absence or in the presence of TMAO (100 μM - incubated for 30 min) in order to evaluate contraction and endothelium dependent relaxation of the SMA. PE induced similar contractions of the SMA in lean and db/db mice and neither the potency nor the maximal response (E MAX ) to PE was affected in the presence of TMAO in both strains. On the other hand, there was a decrease in the potency (pEC 50 : 7.61 ± 0.19 lean; 6.67 ± 0.25 db/db; n=6) and E MAX (9.73 ± 0.43 mN lean; 8.41 ± 0.62 mN db/db; n=6) to ACh in the SMA of db/db mice. TMAO led to a decrease the E MAX to ACh in both strains (7.52 ± 0.43 and 5.46 ± 0.46, for lean and db/db respectively) and the potency of ACh only in lean mice (pEC 50 : 6.01 ± 0.15 and 6.13 ± 0.24, for lean and db/db respectively) when compared to the respective control in the absence of TMAO. In conclusion, TMAO may contribute to the development of cardiovascular complications by impairing the vascular relaxation.