Tsai Yu-Hwai, Ohkita Mamoru, Gariepy Cheryl E
Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor 48109, USA.
Exp Biol Med (Maywood). 2006 Jun;231(6):813-7.
Vascular endothelin (ET)-1 is upregulated in several forms of salt-induced hypertension. It is unclear to what extent these effects are primary or secondary to endothelial damage. We hypothesized that a high-sodium diet (HNa) increases vascular ET-1 production independent of arterial blood pressure changes. We investigated the effect of chronic HNa with and without ET(A) blockade on circulating and aortic ET-1 protein levels as well as aortic expression of ET-1 and ET(A) messenger RNA (mRNA) in inbred Wistar-Kyoto (WKY) and congenic ET(B)-deficient rats. Comparing WKY rats fed a low-sodium diet (LNa) with those fed HNa for 3 weeks, aortic wall ET-1 protein is significantly increased in response to HNa (331 +/- 43 pg/g tissue for LNa vs. 557 +/- 34 pg/gm tissue for HNa). HNa also increased aortic wall ET-1 mRNA levels by 40%, as determined by quantitative reverse transcriptase polymerase chain reaction. We then compared rats chronically treated with the ET(A)-selective antagonist, ABT-627, while receiving either LNa or HNa. There were no differences in arterial blood pressure (mean arterial pressure 89 +/- 1 mm Hg for WKY on LNa; 90 +/- 3 for WKY on HNa; 91 +/- 2 for ET(B)-deficient/ABT-627-treated on HNa) or heart rate. However, aortic wall ET-1 protein levels were 4-fold higher in the HNa group. Further, HNa increased aortic wall ET-1 mRNA (approximately 1.5- to 3-fold) and ET(A) mRNA (approximately 2- to 7-fold), independent of activation of ET(B). Therefore, the expression of ET-1 mRNA by the aortic wall is increased in response to chronic high dietary sodium in WKY rats in the absence of changes in arterial blood pressure.
血管内皮素（ET）-1在多种盐诱导的高血压形式中上调。目前尚不清楚这些作用在多大程度上是内皮损伤的原发性或继发性结果。我们假设高钠饮食（HNa）会增加血管ET-1的产生，而与动脉血压变化无关。我们研究了慢性HNa饮食伴或不伴ET（A）阻断对近交系Wistar-Kyoto（WKY）大鼠和同源ET（B）缺陷大鼠循环和主动脉ET-1蛋白水平以及ET-1和ET（A）信使核糖核酸（mRNA）的主动脉表达的影响。将喂食低钠饮食（LNa）3周的WKY大鼠与喂食HNa的大鼠进行比较，主动脉壁ET-1蛋白因HNa而显著增加（LNa组为331±43 pg/g组织，HNa组为557±34 pg/g组织）。通过定量逆转录聚合酶链反应测定，HNa还使主动脉壁ET-1 mRNA水平增加了40%。然后，我们比较了长期用ET（A）选择性拮抗剂ABT-627治疗的大鼠，这些大鼠同时接受LNa或HNa饮食。动脉血压（LNa饮食的WKY大鼠平均动脉压为89±1 mmHg；HNa饮食的WKY大鼠为90±3 mmHg；HNa饮食且经ET（B）缺陷/ABT-627治疗的大鼠为91±2 mmHg）或心率没有差异。然而，HNa组的主动脉壁ET-1蛋白水平高4倍。此外，HNa增加了主动脉壁ET-1 mRNA（约1.5至3倍）和ET（A）mRNA（约2至7倍），与ET（B）的激活无关。因此，在WKY大鼠中，在动脉血压无变化的情况下，慢性高钠饮食会导致主动脉壁ET-1 mRNA表达增加。
