School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia.
Br J Nutr. 2012 Jan;107(2):218-28. doi: 10.1017/S0007114511002716. Epub 2011 Jun 30.
The present study explored the hypothesis that a prolonged 8 weeks exposure to a high fructose intake suppresses adrenergic and angiotensin II (Ang II)-mediated vasoconstriction and is associated with a higher contribution of α1D-adrenoceptors. A total of thirty-two Sprague-Dawley rats received either 20 % fructose solution (FFR) or tap water (control, C) to drink ad libitum for 8 weeks. Metabolic and haemodynamic parameters were assessed weekly. The renal cortical vasoconstrictor responses to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II were determined in the presence and absence of BMY7378 (α1D-adrenoceptor antagonist). FFR had increased blood pressure, plasma levels of glucose, TAG and insulin. FFR expressed reduced renal vascular responses to adrenergic agonists and Ang II (NA: 50 %, PE: 50 %, ME, 65 %, Ang II: 54 %). Furthermore in the C group, the magnitude of the renal cortical vasoconstriction to all agonists was blunted in the presence of the low or high dose of BMY7378 (NA: 30 and 31 %, PE: 23 and 33 %, ME: 19 and 44 %, Ang II: 53 and 77 %), respectively, while in the FFR, vasoconstriction was enhanced to adrenergic agonists and reduced to Ang II (NA: 8 and 83 %, PE: 55 %, ME, 2 and 177 %, Ang II: 61 and 31 %). Chronic high fructose intake blunts vascular sensitivity to adrenergic agonists and Ang II. Moreover, blocking of the α1D-adrenoceptor subtype results in enhancement of renal vasoconstriction to adrenergic agonists, suggesting an inhibitory action of α1D-adrenoceptors in the FFR. α1D-Adrenoceptors buffer the AT1-receptor response in the renal vasculature of normal rats and fructose feeding suppressed this interaction.
长期 8 周摄入高果糖会抑制肾上腺素能和血管紧张素 II(Ang II)介导的血管收缩,并与 α1D-肾上腺素能受体的贡献增加有关。32 只 Sprague-Dawley 大鼠自由饮用 20%果糖溶液(FFR)或自来水(对照,C)8 周。每周评估代谢和血液动力学参数。在存在和不存在 BMY7378(α1D-肾上腺素能受体拮抗剂)的情况下,确定肾皮质对去甲肾上腺素(NA)、苯肾上腺素(PE)、甲氧胺(ME)和 Ang II 的血管收缩反应。FFR 血压、血糖、TAG 和胰岛素水平升高。FFR 表达对肾上腺素能激动剂和 Ang II 的肾血管反应降低(NA:50%,PE:50%,ME:65%,Ang II:54%)。此外,在 C 组中,在低剂量或高剂量 BMY7378 存在下,所有激动剂引起的肾皮质血管收缩幅度均减弱(NA:30%和 31%,PE:23%和 33%,ME:19%和 44%,Ang II:53%和 77%),而在 FFR 中,对肾上腺素能激动剂的血管收缩增强,对 Ang II 的血管收缩减弱(NA:8%和 83%,PE:55%,ME:2%和 177%,Ang II:61%和 31%)。慢性高果糖摄入会使血管对肾上腺素能激动剂和 Ang II 的敏感性降低。此外,阻断 α1D-肾上腺素能受体亚型会增强肾皮质对肾上腺素能激动剂的血管收缩,表明 FFR 中 α1D-肾上腺素能受体具有抑制作用。α1D-肾上腺素能受体缓冲正常大鼠肾血管中 AT1 受体的反应,而果糖喂养抑制了这种相互作用。