Dietary fats shift mechanisms underlying vasodilation to acetylcholine

Dietary fatty acids may be an effective target for reversing vascular abnormalities associated with diet‐induced obesity. We tested the hypothesis that dietary fats modify mechanisms underlying vascular responses by altering membrane composition and the contribution from nitric oxide synthase (NOS) and cyclooxygenase (Cox) in vascular responses. We fed male mice (C57BL/6J) normal (13% kcal fat) or a high saturated fat diet from lard (HF, 60% kcal fat) for 12 weeks before substituting half of the saturated fats with n‐3 polyunsaturated fatty acid enriched menhaden oil (MO) while still maintaining the same total kcal from fat. After an additional 6‐9 weeks, weights of mice on HF and MO‐enriched diets were similar and more than normal diet mice. MO‐enriched diet increased percentage of n‐3 long chain fatty acids DHA and EPA over three fold in aorta and the unsaturation index (1.07±0.03 vs 1.63±0.14, p<0.05). Relaxation to acetylcholine (ACh) was similar in aorta from all groups but was reduced by inhibition of NOS only in normal and high fat and not MO fed mice. Inhibition of Cox had no effect on aortic responses in any group. ACh responses were not different in gracilis arteries from HF but enhanced in MO compared to normal diet mice. Inhibition of NOS reduced ACh relaxation only in normal and MO fed mice, but Cox contributed to dilation to ACh in gracilis arteries in MO mice. Relaxation to nitroprusside was not affected by diet. Despite shifts in the contribution from NOS versus Cox in responses, diet did not affect total expression of endothelial NOS or Cox1 in arteries from either group. We conclude that a diet high in unsaturated n‐3 fatty acids improved small artery vascular responses but not large artery, in part, through an increase in the Cox contribution.