Endothelial dysfunction of the mesenteric arteries of rats in the early obesity induced by high-fat diet

Background: Disturbance of the morphological and functional properties of the vascular bed in obesity are a serious clinical problem. Basis to their development is endothelial dysfunction. The developed models of obesity in animals using various diets indicate a change in vascular reactivity, howeve...

Full description

Bibliographic Details
Main Author: M. N. Pankova
Format: Article
Language:English
Published: Endocrinology Research Centre 2022-09-01
Series:Ожирение и метаболизм
Subjects:
Online Access:https://www.omet-endojournals.ru/jour/article/view/12842
_version_ 1797204514874327040
author M. N. Pankova
author_facet M. N. Pankova
author_sort M. N. Pankova
collection DOAJ
description Background: Disturbance of the morphological and functional properties of the vascular bed in obesity are a serious clinical problem. Basis to their development is endothelial dysfunction. The developed models of obesity in animals using various diets indicate a change in vascular reactivity, however, questions about the stage at which this occurs and what mechanisms are involved in this process remain open, while they are decisive for choosing the correct tactics for correcting dysfunctions.Aim: The aim of the present study is to determine the changes in acetylcholine (ACh)-induced vasodilation of isolated arteries from rats after six weeks of administration of a high-fat diet (HFD).Materials and methods: The experiments were performed on  Sprague-Dawley males, which at the age of 8 weeks were divided into 2 experimental groups that were treated for the next 6 weeks in the following manner: 1 - control) with standard dry food; 2 - a group fed with a HFD, the total amount of fat in which was 50%. At finish of the diet, the degree of obesity, biochemical parameters in the blood, and blood pressure were measured. Intravital microscopy of the rat mesentery with video recording was used to study the reactivity of the vessels. The contractile and relaxant responses of the vessels were determined by changes in their diameter.Results: The rats after treatment with the HFD (n=15) had higher body weight and amount of visceral fat, significantly increased blood triglycerides, moderate increases in glucose level in blood and systolic pressure compared with the control (n=15). Relaxation responses of mesenteric arteries, having a diameter of 140 to 300 μm in PSS, were recorded after precontraction by phenylephrine. A decrease in ACh-induced vasorelaxation was obtained, which manifests itself before the development of significant changes in carbohydrate metabolism. Incubation of drugs with the inhibitor of endothelial NO synthase L-NAME led to a pronounced weakening of relaxation in animals on a standard diet, and had little effect on vasodilation in the arteries of rats with the HFD. Vasodilation induced by the administration of sodium nitroprusside (NO donor) did not differ significantly in control and experimental animals, which indicates that the sensitivity of vascular smooth muscle to NO remained practically unchanged. ACh-induced relaxation of arteries in dietary rats did not change when the cyclooxygenase pathway was blocked by diclofenac.Conclusion: Functional changes in the contractile activity of the mesenteric arteries, manifested in the form of a decrease in ACh-induced vasorelaxation, occur after treatment with the HFD when animals had an early stage of obesity development before the onset of pronounced disorders of carbohydrate metabolism. This decrease is mainly due to the disruption of the NO-dependent mechanism underlying ACh-induced relaxation in the norm.
first_indexed 2024-03-08T09:11:59Z
format Article
id doaj.art-1b7c7dd3a26a40dab195a3250c9efe33
institution Directory Open Access Journal
issn 2071-8713
2306-5524
language English
last_indexed 2024-04-24T08:36:27Z
publishDate 2022-09-01
publisher Endocrinology Research Centre
record_format Article
series Ожирение и метаболизм
spelling doaj.art-1b7c7dd3a26a40dab195a3250c9efe332024-04-16T16:16:14ZengEndocrinology Research CentreОжирение и метаболизм2071-87132306-55242022-09-0119215816510.14341/omet1284210926Endothelial dysfunction of the mesenteric arteries of rats in the early obesity induced by high-fat dietM. N. Pankova0Pavlov Institute of Physiology of the Russian Academy of SciencesBackground: Disturbance of the morphological and functional properties of the vascular bed in obesity are a serious clinical problem. Basis to their development is endothelial dysfunction. The developed models of obesity in animals using various diets indicate a change in vascular reactivity, however, questions about the stage at which this occurs and what mechanisms are involved in this process remain open, while they are decisive for choosing the correct tactics for correcting dysfunctions.Aim: The aim of the present study is to determine the changes in acetylcholine (ACh)-induced vasodilation of isolated arteries from rats after six weeks of administration of a high-fat diet (HFD).Materials and methods: The experiments were performed on  Sprague-Dawley males, which at the age of 8 weeks were divided into 2 experimental groups that were treated for the next 6 weeks in the following manner: 1 - control) with standard dry food; 2 - a group fed with a HFD, the total amount of fat in which was 50%. At finish of the diet, the degree of obesity, biochemical parameters in the blood, and blood pressure were measured. Intravital microscopy of the rat mesentery with video recording was used to study the reactivity of the vessels. The contractile and relaxant responses of the vessels were determined by changes in their diameter.Results: The rats after treatment with the HFD (n=15) had higher body weight and amount of visceral fat, significantly increased blood triglycerides, moderate increases in glucose level in blood and systolic pressure compared with the control (n=15). Relaxation responses of mesenteric arteries, having a diameter of 140 to 300 μm in PSS, were recorded after precontraction by phenylephrine. A decrease in ACh-induced vasorelaxation was obtained, which manifests itself before the development of significant changes in carbohydrate metabolism. Incubation of drugs with the inhibitor of endothelial NO synthase L-NAME led to a pronounced weakening of relaxation in animals on a standard diet, and had little effect on vasodilation in the arteries of rats with the HFD. Vasodilation induced by the administration of sodium nitroprusside (NO donor) did not differ significantly in control and experimental animals, which indicates that the sensitivity of vascular smooth muscle to NO remained practically unchanged. ACh-induced relaxation of arteries in dietary rats did not change when the cyclooxygenase pathway was blocked by diclofenac.Conclusion: Functional changes in the contractile activity of the mesenteric arteries, manifested in the form of a decrease in ACh-induced vasorelaxation, occur after treatment with the HFD when animals had an early stage of obesity development before the onset of pronounced disorders of carbohydrate metabolism. This decrease is mainly due to the disruption of the NO-dependent mechanism underlying ACh-induced relaxation in the norm.https://www.omet-endojournals.ru/jour/article/view/12842endothelial dysfunctionobesityrat mesenteric arteries
spellingShingle M. N. Pankova
Endothelial dysfunction of the mesenteric arteries of rats in the early obesity induced by high-fat diet
Ожирение и метаболизм
endothelial dysfunction
obesity
rat mesenteric arteries
title Endothelial dysfunction of the mesenteric arteries of rats in the early obesity induced by high-fat diet
title_full Endothelial dysfunction of the mesenteric arteries of rats in the early obesity induced by high-fat diet
title_fullStr Endothelial dysfunction of the mesenteric arteries of rats in the early obesity induced by high-fat diet
title_full_unstemmed Endothelial dysfunction of the mesenteric arteries of rats in the early obesity induced by high-fat diet
title_short Endothelial dysfunction of the mesenteric arteries of rats in the early obesity induced by high-fat diet
title_sort endothelial dysfunction of the mesenteric arteries of rats in the early obesity induced by high fat diet
topic endothelial dysfunction
obesity
rat mesenteric arteries
url https://www.omet-endojournals.ru/jour/article/view/12842
work_keys_str_mv AT mnpankova endothelialdysfunctionofthemesentericarteriesofratsintheearlyobesityinducedbyhighfatdiet