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妊娠糖尿病在胸主动脉和腹主动脉中的不同影响:内皮和血管紧张素 II 受体的影响。

Divergent impact of gestational diabetes mellitus between the thoracic and abdominal rat aorta: Influence of endothelium and angiotensin II receptors.

机构信息

Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Col. Santo Tomás, México, 11340, D.F, Mexico.

Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Col. Santo Tomás, México, 11340, D.F, Mexico.

出版信息

Eur J Pharmacol. 2021 May 15;899:173981. doi: 10.1016/j.ejphar.2021.173981. Epub 2021 Mar 6.

Abstract

Gestational diabetes mellitus (GDM) affects 5-10% of pregnancies and increases the risk of fetal and maternal adverse outcomes. Interestingly, the vascular response to AngII is decreased by pregnancy while the response is increased by diabetes. It remains unclear how GDM affects vascular tone and how angiotensin II receptors contribute to these changes. In this work, we sought to establish the vascular impact of a hypercaloric diet-induced GDM through changes in AT and AT receptor's expression. Female rats fed for 7 weeks with standard (SD) or hypercaloric (HD) diet were divided at week 4. Half of the rats of each group were mated to become pregnant and those fed with a HD developed GDM. AngII-induced vasoconstriction was measured in thoracic or abdominal aorta rings using a conventional isolated organ bath and AT and AT receptors were searched by immunohistochemistry. Experiments where conducted on the pregnant standard diet group (PSD) and the pregnant hypercaloric-gestational diabetes mellitus group (PHD-GDM). Vasoconstriction was reduced in the thoracic aorta (P < 0.05 vs PSD) but increased in the abdominal aorta of PHD-GDM rats (P < 0.05 vs PSD). Blockade of AT receptors using PD123319 decreased vasoconstriction, particularly in the abdominal aorta of PHD-GDM animals (P < 0.05 vs PSD). PHD-GDM increased AT receptors expression (P < 0.05 vs PSD). Also, PHD-GDM reverted physiologic hypoglycemia and hypotension of healthy pregnancy. Findings provide new insight into the hypercaloric diet induced damage on the vasculature during pregnancy.

摘要

妊娠期糖尿病(GDM)影响 5-10%的妊娠,并增加了胎儿和产妇不良结局的风险。有趣的是,血管对血管紧张素 II(AngII)的反应在妊娠期间降低,而在糖尿病中增加。目前尚不清楚 GDM 如何影响血管张力,以及血管紧张素 II 受体如何促成这些变化。在这项工作中,我们试图通过改变 AT 和 AT 受体的表达来确定高热量饮食诱导的 GDM 对血管的影响。雌性大鼠喂食标准(SD)或高热量(HD)饮食 7 周,在第 4 周分组。每组一半的大鼠交配怀孕,那些喂食高热量饮食的大鼠发生 GDM。使用常规离体器官浴测量胸主动脉或腹主动脉环对 AngII 诱导的血管收缩,并通过免疫组织化学搜索 AT 和 AT 受体。实验在怀孕标准饮食组(PSD)和怀孕高热量-妊娠期糖尿病组(PHD-GDM)中进行。胸主动脉的血管收缩减少(PSD 相比,P<0.05),但 PHD-GDM 大鼠的腹主动脉血管收缩增加(PSD 相比,P<0.05)。使用 PD123319 阻断 AT 受体可减少血管收缩,特别是 PHD-GDM 动物的腹主动脉血管收缩(PSD 相比,P<0.05)。PHD-GDM 增加了 AT 受体的表达(PSD 相比,P<0.05)。此外,PHD-GDM 逆转了健康妊娠的生理性低血糖和低血压。这些发现为高热量饮食在妊娠期间对血管的损害提供了新的见解。

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