High fat diet alters endothelium dependent responses in isolated mouse aortic rings and increases their sensitivity to cytokine-induced endothelial dysfunction

We previously demonstrated that intravenous lipopolysaccharide administration in mice fed a high fat diet (HFD) resulted in an exacerbated production of the pro-inflammatory cytokines TNFα and IL-6 in serum. Therefore, we tested whether vascular reactivity in isolated aortic rings was affected by mice fed a HFD. Therefore, C57BL/6 mice were fed either a normal diet (ND) or a HFD for two weeks, and the vascular response to acetylcholine (ACh, 10-9-10-6 M), sodium nitroprusside (SNP, 10-10-10-7 M) and phenylephrine (Phe, 10-6 M) were compared under control and cytokine-stimulated conditions (24hr, 37°C, TNFα, IL-1β, IFNγ ). HFD significantly increased the vascular response to ACh, but not SNP or Phe, compared to ND. Under cytokine stimulated conditions, the vascular response to ACh was significantly decreased in both HFD and ND groups, but the magnitude of the shift in the EC50 was much greater in the HFD than the ND group (50-fold vs. 7-fold). In addition, the contractile response to Phe was increased appr...