Awad Azza S
Department of Pharmacology and Toxicology, Faculty Pharmacy, Al-Azhar University (Girls), Nasr City, Cairo, Egypt.
Vascul Pharmacol. 2006 Sep;45(3):141-7. doi: 10.1016/j.vph.2006.04.004. Epub 2006 Jul 31.
The precise mechanisms of vascular diseases in patients with diabetic hypertensive are not clearly understood. There are evidences of alteration in permeability of blood-brain barrier (BBB) in diabetic hypertensive rats. This study sought to examine the effect of candesartan on the systolic blood pressure and the brain endothelial barrier function and antioxidant enzymes in rat brain. Five groups of eight male Sprague-Dawley rats include: control group (gpI), diabetic hypertensive group (gpII), diabetic hypertensive group treated with candesartan (gpIII), diabetic hypertensive rats with epinephrine (gpIV) and diabetic hypertensive rats with epinephrine treated with candesartan (gpV). Diabetes was induced by single injection of 55 mg kg(-1) streptozotocin (STZ) i.p. Blood glucose was measured, rats with blood glucose higher than 300 mg/dl were identified as diabetic. After induction of diabetes, rats received L-NAME (0.5 mg/ml in drinking water for 1 week) starting on the day 4 after STZ injection. Systolic blood pressure (SBP) was recorded two times, at day 0 (before starting L-NAME) and at day 7 (after L-NAME treatment). Also, body weight was measured two times, at initial time (before STZ injection) and terminal (at the last day in the experiment). On the day of acute experiment, rats were anesthetized with sodium pentobarbital (35 mg/kg, i.p.). The integrity of the BBB was investigated using Evans blue (EB) dye (4 ml/kg, 2%). Epinephrine was used (40 micro g/kg) to increase the permeability of the brain. After decapitation, first the brain was removed, next homogenized and then the content of EB dye in the brain was measured. Another five groups of rats manipulated with the same manner except EB dye injection. These second group to evaluate antioxidant enzymes, reduced glutathione (GSH), lipid peroxides and superoxide dismutase (SOD) in brain homogenate. This study indicates that, in diabetic hypertensive rats, epinephrine administration leads to increase in microvascular-EB-albumin efflux to brain. However, candesartan treatment significantly attenuates this permeability to brain tissue and significantly increased GSH and SOD activity, while level of lipid peroxides was decreased significantly. The finding supports that the use of candesartan may offer a good alternative in the treatment of diabetic hypertensive subjects because it has an action that might be mediated through an antioxidant effect and beneficial effects on vascular endothelial permeability as well.
糖尿病高血压患者血管疾病的确切机制尚不清楚。有证据表明糖尿病高血压大鼠血脑屏障（BBB）的通透性发生了改变。本研究旨在探讨坎地沙坦对大鼠收缩压、脑内皮屏障功能及脑内抗氧化酶的影响。五组，每组八只雄性Sprague-Dawley大鼠，包括：对照组（第一组）、糖尿病高血压组（第二组）、用坎地沙坦治疗的糖尿病高血压组（第三组）、用肾上腺素处理的糖尿病高血压大鼠（第四组）和用肾上腺素处理并用坎地沙坦治疗的糖尿病高血压大鼠（第五组）。通过腹腔注射55 mg/kg链脲佐菌素（STZ）单次诱导糖尿病。测量血糖，血糖高于300 mg/dl的大鼠被确定为糖尿病大鼠。糖尿病诱导后，大鼠从注射STZ后的第4天开始饮用含L-NAME（0.5 mg/ml）的水1周。在第0天（开始饮用含L-NAME的水之前）和第7天（L-NAME治疗后）记录收缩压（SBP）两次。此外，在初始时间（注射STZ前）和末期（实验的最后一天）测量体重两次。在急性实验当天，用戊巴比妥钠（35 mg/kg，腹腔注射）麻醉大鼠。使用伊文思蓝（EB）染料（4 ml/kg，2%）研究BBB的完整性。使用肾上腺素（40 μg/kg）增加脑通透性。断头后，首先取出大脑，然后匀浆，接着测量脑中EB染料的含量。另外五组大鼠以相同方式处理，但不注射EB染料。第二组用于评估脑匀浆中的抗氧化酶、还原型谷胱甘肽（GSH）、脂质过氧化物和超氧化物歧化酶（SOD）。本研究表明，在糖尿病高血压大鼠中，给予肾上腺素会导致微血管-EB-白蛋白向脑内的流出增加。然而，坎地沙坦治疗可显著减弱脑组织的这种通透性，并显著提高GSH和SOD活性，同时脂质过氧化物水平显著降低。这一发现支持坎地沙坦的使用可能为糖尿病高血压患者的治疗提供一个良好的选择，因为它可能通过抗氧化作用以及对血管内皮通透性的有益作用来发挥功效。
