Chronic high-sodium diet increases aortic wall endothelin-1 expression in a blood pressure-independent fashion in rats.
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.
Tsai
Yu-Hwai
YH
Department of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor 48109, USA.
Ohkita
Mamoru
M
Gariepy
Cheryl E
CE
D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D012982:Sodium, Dietary / Q000008:administration & dosage* / Q000494:pharmacology
D019332:Endothelin-1; D012333:RNA, Messenger; D012982:Sodium, Dietary