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

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Abstract

High-fat diet (HFD) can lead to the development of metabolic syndrome (MS). However, the issue of the mechanisms underlying pathophysiological processes in MS has not been studied enough. The aim of the work was to study in vivo the effect of a high-fat diet (HFD) on the reactivity of the mesenteric arteries in Wistar rats, as well as to evaluate a change of the mechanisms of endothelium-dependent arterial dilation in HFD. The HFD group of rats (n = 25) were fed on a HFD containing 50% animal fat for 10 weeks, while the control group (n = 25) received a standard diet. The effect of HFD on endothelium-dependent and endothelium-independent responses of the mesenteric arteries exposed to agonists in the absence and presence of the blockers of NO synthase (L-NAME), cyclooxygenase (indomethacin), and K+ channels (tetraethylammonium) was assessed using photomicrography and in vivo video registration of the mesenteric artery diameter. HFD led to the development of MS, including dyslipidemia, hyperglycemia and insulin resistance, and an increase in blood pressure. MS was accompanied by a functional impairment of the mesenteric arteries. In the HFD vs. control group, there was a 29% increase in the constrictor response to phenylephrine, as well as a 36% decrease in the reactivity of phenylephrine-preconstricted vessels exposed to acetylcholine (ACh). In the HFD group, preincubation of vessels with blockers reduced the amplitude of ACh-induced vasorelaxation compared to the baseline ACh-induced vasorelaxation: 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 sodium nitroprusside-induced vasodilation. Thus, endothelial dysfunction in HFD-exposed rats was mediated both by the impairment of NO-dependent mechanisms of vasodilation (specifically, by a decrease in endothelial NO production) and by a decrease in the efficiency of BKСа channels. Decreased NO bioavailability in HFD was partially compensated by the activation of the mechanisms of IKCa- and SKCa-mediated endothelium-dependent hyperpolarization in ACh-induced vasodilation.

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Funding

This work was supported by the State Program 47 SP “Scientific and Technological Development of the Russian Federation” (2019–2030), theme reg. no. 0134-2019-0001.

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  1. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia

    G. T. Ivanova

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Correspondence to G. T. Ivanova.

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All manipulations with animals complied with the principles of the Basel Declaration and were approved by the Ethics Committee of Pavlov Institute of Physiology (Russian Academy of Sciences).

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The author declares that she has neither evident nor potential conflict of interest that might be related with the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 1, pp. 61–74https://doi.org/10.31857/S0869813923010089.

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Ivanova, G.T. Reactivity of Mesenteric Arteries in the Development of Metabolic Syndrome in Rats Fed on a High-Fat Diet. J Evol Biochem Phys 59, 154–164 (2023). https://doi.org/10.1134/S0022093023010131

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