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
Vascular responses to reactive oxygen species (ROS)/hydroxyl radical (.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/.OH-induced a rapid, transient vasodilation. In the carotid, but not in femoral artery, ROS/.OH-induced dilation increased with increasing dietary fat intake (P < 0.05 vs. LF diet), while contractile responses to ROS/.OH remained unaffected. In femoral arteries, ROS/.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).


CONCLUSIONS
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.
Bhattacharya
Indranil
I
Department of Medicine, Internal Medicine I, Medical Policlinic, University Hospital, Zürich, Switzerland.
Mundy
Alexa L
AL
Widmer
Corinne C
CC
Kretz
Martin
M
Barton
Matthias
M
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D004041:Dietary Fats / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D004041:Dietary Fats; D019332:Endothelin-1; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D017665:Hydroxyl Radical; D000109:Acetylcholine