Mechanism of impaired baroreflex sensitivity in Wistar rats fed a high-fat and -carbohydrate diet

Mechanism of impaired baroreflex sensitivity in Wistar rats fed a high-fat and -carbohydrate diet
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DOI:
10.1017/s0007114510000450
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发表时间:
2010-07-28
影响因子:
3.6
通讯作者:
Yang, Baofeng
Yang, Baofeng
中科院分区:
医学3区
文献类型:
--
作者:
Ai, Jing;Liang, Feng;Yang, Baofeng

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高脂肪和高碳水化合物饮食都被认为与压力反射敏感性受损有关。然而,其机制尚不清楚。在本研究中,研究了复杂的高脂肪和高碳水化合物饮食(HFCD)对压力反射回路的影响。配制HFCD乳剂并口服给药于大鼠30 d。然后将大鼠麻醉,并在静脉注射不同剂量的苯肾上腺素(PE)和硝普钠(SNP)后测量压力反射敏感性。透射电镜观察脑干形态学变化。通过定量RT-PCR和Western blot分析测定压力反射敏感性相关基因和蛋白的表达。我们发现:(1)HFCD可显著降低PE引起的动脉血压升高的心率反应,但对SNP引起的动脉血压降低的心率反应无影响;(2)HFCD可引起延髓鞘增厚、有髓神经萎缩和透明质溶解;(3)可引起P物质、降钙素基因相关肽蛋白水平的变化。GlutR 2和γ-氨基丁酸A受体都显着减少与HFCD管理的大鼠脑干。这些发现表明HFCD可损害大鼠的压力感受性反射敏感性。孤束核和疑核的形态重塑和神经递质和受体的减少参与了这一过程。
Both high-fat and high-carbohydrate diets have been considered in association with the impairment of baroreflex sensitivity. However, the mechanisms are unclear. In the present study, the effects of a complex high-fat and high-carbohydrate diet (HFCD) on baroreflex circuitry were investigated. A HFCD emulsion was formulated and orally administered to rats for 30 d. Rats were then anaesthetised and baroreflex sensitivity was measured following intravenous injection of phenylephrine (PE) and sodium nitroprusside (SNP) at various doses. Morphological changes of the brainstem were detected by transmission electron microscopy. Baroreflex sensitivity-associated gene and protein expression was determined by quantitative RT-PCR and Western blot analysis. We found that: (1) the HFCD significantly attenuated heart rate responses to arterial blood pressure (ABP) increases induced by PE, but had no effect on heart rate responses to ABP decreases induced by SNP; (2) the HFCD induced medullary sheath thickening, myelinated nerve atrophy and hyaloplasm dissolving; (3) protein levels of substance P, calcitonin gene-related peptide. GlutR2 and gamma-aminobutyric acid A receptors were all markedly decreased in the brainstems of rats administered with the HFCD. These findings conclude that a HFCD could impair the baroreflex sensitivity of rats. Remodelled morphology and decreased neuro-transmitters and receptors in the domains of the nucleus tractus solitarii and nucleus ambiguus are participating in this process.