Department of Internal Medicine II, Regensburg University Medical Center, Germany.
Cardiovasc Diabetol. 2011 Oct 18;10:94. doi: 10.1186/1475-2840-10-94.
Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF). Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet.
After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28%) or a high-salt diet (5.5%) starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food) (ZDF+S+E), hydralazine (25 mg/kg per day) (ZDF+S+H), or no treatment (ZDF+S). Rats on normal salt-diet were assigned to eplerenone (ZDF+E) or no treatment (ZDF). Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL) or high-salt diet (ZL+S) serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio) and vascular stiffness (strain and stress) were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed.
Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition with less resistant components. This indicates increased vascular stiffness in salt-loaded ZDF rats, which could be prevented by eplerenone but not by hydralazine. Collagen content was increased in ZL and ZDF rats on high-salt diet. Eplerenone and hydralazine prevented the increase of collagen content. There was no difference in elastin content.
Eplerenone and hydralazine prevented increased media-to-lumen ratio in salt-loaded ZDF-rats, indicating a regression of vascular hypertrophy, which is likely mediated by the blood pressure lowering-effect. Eplerenone has additionally the potential to prevent increased vascular stiffness in salt-loaded ZDF-rats. This suggests an effect of the specific aldosterone antagonist on adverse vascular wall remodelling.
在 2 型糖尿病模型大鼠（Zucker 糖尿病肥胖大鼠，ZDF）中，醛固酮水平升高。此外，ZDF 大鼠的血压对盐敏感。本研究的目的是研究醛固酮拮抗剂依普利酮对 ZDF 大鼠正常和高盐饮食下阻力血管的结构和力学特性的影响。
在糖尿病发展后，15 周龄时，ZDF 动物开始分别接受正常盐饮食（0.28%）或高盐饮食（5.5%）。高盐饮食的 ZDF 大鼠随机分为依普利酮（100mg/kg/天，食物中）（ZDF+S+E）、肼屈嗪（25mg/kg/天）（ZDF+S+H）或无治疗（ZDF+S）组。接受正常盐饮食的 ZDF 大鼠分为依普利酮组（ZDF+E）或无治疗组（ZDF）。正常血糖的 Zucker 瘦大鼠也分为接受正常（ZL）或高盐饮食（ZL+S）的两组，作为对照组。通过尾套法测量收缩压。实验在 25 周龄时结束。在加压肌动描记器上研究肠系膜阻力血管。具体来说，分析血管肥大（中膜与腔比）和血管僵硬（应变和应力）。加压固定后，进行胶原和弹性蛋白含量的组织学分析。
与 ZDF 相比，盐负荷的 ZDF 血压明显升高。依普利酮和肼屈嗪的降压作用相似，但未达到统计学意义。与 ZDF 和 ZL 相比，ZDF+S 中的肠系膜阻力血管的中膜与腔比显著增加。依普利酮和肼屈嗪均可预防盐诱导的血管肥大。与 ZL 和 ZDF+S+E 相比，盐负荷的 ZDF 大鼠的应变曲线明显降低，但与 ZDF+S+H 相比无差异。依普利酮而非肼屈嗪使应变-应力曲线向右移动，表明血管壁组成中阻力成分减少。这表明盐负荷的 ZDF 大鼠的血管僵硬增加，依普利酮可预防，但肼屈嗪不能预防。ZL 和高盐饮食的 ZDF 大鼠的胶原含量增加。依普利酮和肼屈嗪可预防胶原含量的增加。弹性蛋白含量无差异。
依普利酮和肼屈嗪可预防盐负荷的 ZDF 大鼠中膜与腔比的增加，表明血管肥大的消退，这可能是通过降压作用介导的。依普利酮还有预防盐负荷的 ZDF 大鼠血管僵硬增加的潜力。这表明特定的醛固酮拮抗剂对不良血管壁重塑有作用。
