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VASCULAR AND HYPERTENSION

Chronic High-Sodium Diet Increases Aortic Wall Endothelin-1 Expression in a Blood Pressure–Independent Fashion in Rats

Yu-Hwai Tsai^*, Mamoru Ohkita^*,1 and Cheryl E. Gariepy^*,,2

^* Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor, Michigan 48109; and C. S. Mott Children’s Hospital, Ann Arbor, Michigan 48109

To whom requests for reprints should be addressed at ² Rm A520B, 1150 W. Medical Center Drive, Medical Science Research Building I, Ann Arbor, MI 48108-0656. E-mail: cgariepy{at}med.umich.edu

Abstract

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 (~1.5- to 3-fold) and ET_A mRNA (~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.

Key Words: hypertension • salt-sensitive • endothelin-A receptor • antagonist • artery • expression