Regional heterogeneity of functional changes in conduit arteries after high-fat diet

Objective: To determine effects of dietary fat content on vascular responses in different conduit arteries in mice. Methods and Procedures: Vascular responses to reactive oxygen species ( ROS)/ hydroxyl radical (center dot OH), acetylcholine ( ACh), endothelin-1 ( ET-1), and angiotensin II ( Ang II) were determined in carotid and femoral arteries of C57BL/ 6J mice fed with diets varying in fat content ( low fat ( LF), 12.3%; high fat ( HF), 41%; and very high fat ( VHF), 58% ( kcal from fat)) for 15 weeks, beginning at 4 weeks of age. Results: In precontracted rings of carotid and femoral artery, ROS/center dot OH-induced a rapid, transient vasodilation. In the carotid, but not in femoral artery, ROS/center dot OH-induced dilation increased with increasing dietary fat intake ( P < 0.05 vs. LF diet), while contractile responses to ROS/center dot OH remained unaffected. In femoral arteries, ROS/center dot OH-induced contractions were reversed into relaxations after both HF and VHF diet ( P < 0.05 vs. LF diet). Both ET-1 and Ang II induced strong contractions in the femoral artery that were unaffected by dietary fat intake. In contrast, in the carotid artery Ang II-induced contraction was attenuated after HF and VHF diets ( P < 0.005 vs. LF diet), whereas ET-1-induced vasoconstriction was significantly increased ( P < 0.05 VHF vs. LF and HF). Treatment with VHF diet enhanced ACh-mediated endothelium-dependent relaxation only in the femoral artery ( P < 0.05 vs. HF). Discussion: These findings demonstrate that dietary fat content has regional and distinct effects on vascular function in different vascular beds. The data also suggest the possibility that in selected conduit arteries ROS-dependent vasodilator mechanisms become activated in response to increased dietary fat intake.