Reduction of eNOS in Vascular Smooth Muscle by Salt Independently of Hypertension.

Natalia L. Rukavina Mikusic, María I. Rosón, Silvana L. Della Penna, Marcelo R Choi, Susana Gorzalczany, Elsa Zotta, Jorge E Toblli, Belisario E Fernández
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Abstract

Background: Endothelial nitric oxide synthase (eNOS) is known to be expressed in endothelium and smooth muscle cells of arteries. The aim of this study was to investigate the expression of eNOS in intimal and medial layer of aorta from rats fed with a high salt diet and its modulation by losartan and tempol.

Methods: Rats were fed during three weeks with: normal salt diet (NS, 0.4% NaCl); high salt diet (HS, 8% NaCl); NS plus tempol 1 mM (NS-T); HS plus tempol (HS-T); NS plus losartan 40mg.kg-1 (NS-L) and HS plus losartan (HS-L). Systolic blood pressure was recorded by the tail cuff method. Rats were then anaesthetized and the thoracic aorta and small arteries (bronchial branches of aorta) were processed to evaluate the expression of eNOS and aquaporin-1 (AQP-1) by immunohistochemistry.

Results: HS group showed increased systolic blood pressure, increased eNOS and AQP-1 immunoexpression in the aorta intimal layer, and decreased eNOS immunoexpression in the aorta medial layer, respect to NS group. Losartan and tempol prevented hypertension and changes in the expression of eNOS and AQP-1 of the intimal layer. However, only tempol increased the expression of eNOS elicited by sodium overload in the medial layer of the aorta and small arteries respect to HS group.

Conclusions: A high salt diet decreases eNOS expression in vascular smooth muscle layers of aorta and small arteries, which is reversed by tempol. These results suggest an adverse effect of oxidative stress on vascular eNOS in rats fed a high salt diet independently of hypertension.

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盐对血管平滑肌中 eNOS 的影响与高血压无关。
背景:已知内皮一氧化氮合酶(eNOS)在动脉内皮细胞和平滑肌细胞中均有表达。本研究旨在调查高盐饮食喂养的大鼠主动脉内膜和内膜层中 eNOS 的表达情况以及洛沙坦和替普莫对其的调节作用:对大鼠进行为期三周的喂养:正常盐饮食(NS,0.4% NaCl);高盐饮食(HS,8% NaCl);NS加1 mM的tempol(NS-T);HS加tempol(HS-T);NS加40mg.kg-1的洛沙坦(NS-L)和HS加洛沙坦(HS-L)。用尾袖带法记录收缩压。然后麻醉大鼠,处理胸主动脉和小动脉(主动脉支气管分支),用免疫组化方法评估 eNOS 和 aquaporin-1 (AQP-1) 的表达:结果:与NS组相比,HS组收缩压升高,主动脉内膜层的eNOS和AQP-1免疫表达增加,主动脉内膜层的eNOS免疫表达减少。洛沙坦和替普莫尔可预防高血压以及主动脉内膜层 eNOS 和 AQP-1 表达的变化。然而,与 HS 组相比,只有 tempol 增加了钠超载引起的主动脉和小动脉内侧层 eNOS 的表达:结论:高盐饮食会降低主动脉和小动脉血管平滑肌层中 eNOS 的表达,而 tempol 可逆转这种情况。这些结果表明,氧化应激对高盐饮食大鼠血管 eNOS 有不利影响,与高血压无关。
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