Protection against oxidative stress in diabetic rats:: Role of angiotensin AT1 receptor and beta 1-adrenoceptor antagonism
Protection against oxidative stress in diabetic rats:: Role of angiotensin AT1 receptor and beta 1-adrenoceptor antagonism
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DOI：
10.1016/j.ejphar.2005.07.020
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发表时间：
2005-09-27
影响因子：
5
通讯作者：
Tschöpe, C
中科院分区：
文献类型：
--
作者：
Dorenkamp, M;Riad, A;Tschöpe, C
氧化应激和低度炎症是糖尿病的标志。我们探讨了血管紧张素 11 I 型 (AT1) 受体拮抗剂坎地沙坦和选择性 I-肾上腺素受体拮抗剂美托洛尔的保护性、与血压无关的作用。 8周大的Sprague-Dawley大鼠注射链脲佐菌素后诱发糖尿病。糖尿病大鼠被随机分配接受亚抗高血压剂量的坎地沙坦或美托洛尔治疗或安慰剂治疗。在股四头肌中，测定了氧化应激和炎症的肌肉组织标志物。在自灌注后肢体内测量固有血管床的功能。 NAD(P)H 活性、其胞质亚基 p22(phox) 和内皮 NO 合酶 e(NOS) 表达的增加显示氧化应激增强。细胞间分子 (ICAM)-1 和血管细胞粘附分子 (VCAM)-1 以及诱导型一氧化氮合酶 (iNOS) 的上调揭示了炎症过程。糖尿病与内皮依赖性和非依赖性血管舒张的严重损害有关。坎地沙坦而非美托洛尔可降低 NAD(P)H 活性，减弱糖尿病诱导的 p22(phox) 和 eNOS mRNA 过度表达以及 ICAM-1、VCAM-1、iNOS 和 eNOS 免疫反应性，并导致内皮依赖性血管舒张功能显着改善（与安慰剂治疗相比，+46.3%；P
Oxidative stress and low-grade inflammation are hallmarks of diabetes mellitus. We explored protective, blood pressure-independent effects of the angiotensin 11 type I (AT,) receptor antagonist candesartan and the selective [ I-adrenoceptor antagonist metoprolol. Diabetes mellitus was induced in 8-week-old Sprague-Dawley rats after injection of streptozotocin. Diabetic rats were randomized to treatment with candesartan or metoprolol in sub-antihypertensive doses or to placebo treatment. In the quadriceps, musculature markers of oxidative stress and inflammation were determined. Function of the inherent vascular bed was measured in vivo in the autoperfused hindlimb. Increases in NAD(P)H activity, expression of its cytosolic subunit p22(phox) and of endothelial NO synthase e(NOS) displayed enhanced oxidative stress. Upregulated intercellular (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 and of inducible NOS (iNOS) revealed inflammatory processes. Diabetes was associated with severe impairment of endothelium-dependent and -independent vasodilatation. Candesartan, but not metoprolol, reduced NAD(P)H activity, attenuated diabetes-induced over-expression of p22(phox) and eNOS mRNA as well as ICAM-1, VCAM-1, iNOS and eNOS imunnoreactivity and led to a substantial improvement of endothelium-dependent vasodilatation (+46.3% vs. placebo treatment; P