Reactivity of Mesenteric Arteries in the Development of Metabolic Syndrome in Rats Fed on a High-Fat Diet

High-fat diet (HFD) can lead to the development of metabolicsyndrome (MS). However, the issue of the mechanisms underlying pathophysiologicalprocesses in MS has not been studied enough. The aim of the workwas to study in vivo the effect of a high-fat diet (HFD) on the reactivityof the mesenteric arteries in Wistar rats, as well as to evaluatea change of the mechanisms of endothelium-dependent arterial dilationin HFD. The HFD group of rats (n =25) were fed on a HFD containing 50% animal fat for 10 weeks, whilethe control group (n = 25)received a standard diet. The effect of HFD on endothelium-dependentand endothelium-independent responses of the mesenteric arteriesexposed to agonists in the absence and presence of the blockersof NO synthase (L-NAME), cyclooxygenase (indomethacin), and K+ channels(tetraethylammonium) was assessed using photomicrography and invivo video registration of the mesenteric artery diameter. HFD ledto the development of MS, including dyslipidemia, hyperglycemiaand insulin resistance, and an increase in blood pressure. MS wasaccompanied by a functional impairment of the mesenteric arteries.In the HFD vs. control group, there was a 29% increase in the constrictor responseto phenylephrine, as well as a 36% decrease in the reactivity ofphenylephrine-preconstricted vessels exposed to acetylcholine (ACh).In the HFD group, preincubation of vessels with blockers reducedthe amplitude of ACh-induced vasorelaxation compared to the baseline ACh-inducedvasorelaxation: with L-NAME by 47%, L-NAME and indomethacin by 50%,L-NAME, indomethacin and tetraethylammonium by 65%; in the controlgroup, by 69, 72 and 83%, respectively. HFD had no significant effecton the amplitude of sodium nitroprusside-induced vasodilation. Thus,endothelial dysfunction in HFD-exposed rats was mediated both bythe impairment of NO-dependent mechanisms of vasodilation (specifically,by a decrease in endothelial NO production) and by a decrease inthe efficiency of BKCa channels. DecreasedNO bioavailability in HFD was partially compensated by the activationof the mechanisms of IKCa- and SKCa-mediatedendothelium-dependent hyperpolarization in ACh-induced vasodilation.