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

Abstract

Higt fat diet can lead to the development of metabolic syndrome (MS). However, the question of the mechanisms of pathophysiological processes in MS has not been studied enough. The aim of the work was to study the effect of a high-fat diet (HFD) on the reactivity of the mesenteric arteries of Wistar rats in vivo, as well as to evaluate the change in the mechanisms of endothelium-dependent arterial dilatation in HFD. The HFD-group of rats (n = 25) received HFD containing 50% animal fat for 10 weeks, the control group (n = 25) received a standard diet. The effect of HFD on endothelium-dependent and endothelium-independent responses of the mesenteric arteries under the action of agonists in the absence and with the use of blockers of NO-synthase (L-NAME), cyclooxygenase (indomethacin), and K+-channels (tetraethylammonium) was assessed using photomicrography and video recording of mesenteric artery diameter in vivo. HFD in rats led to the development of MS, including dyslipidemia, hyperglycemia and insulin resistance, and an increase in blood pressure. MS was accompanied by impaired functional state of the mesenteric arteries. In rats of the HFD group, compared with the control group, there was an increase in the constrictor reaction to phenylephrine by 29%, as well as a decrease in the reactivity of vessels previously contracted by phenylephrine under the action of acetylcholine by 36%. Pre-incubation of vessels with blockers reduced the amplitude of relaxation under the action of acetylcholine, compared with the initial acetylcholine-induced vasorelaxation, in HFD-group rats: with L-NAME – by 47%, L-NAME and indomethacin – by 50%, L-NAME, indomethacin and tetraethylammonium – by 65%; in the control group – by 69, 72 and 83%, respectively. HFD had no significant effect on the amplitude of vasodilation under the action of sodium nitroprusside. Thus, endothelial dysfunction in HFD-treated rats was mediated both by impairment of NO-dependent mechanisms of vasodilation, in particular, by a decrease in NO production by the endothelium, and by a decrease in the effectiveness of ВКСа. The decrease in NO bioavailability in HFD was partially compensated by the activation of endothelial hyperpolarization mechanisms (mediated by IKCa and SKCa activities) in acetylcholine-induced vasodilation.