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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/H2871    most recent 00031.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Takeda, R. Articles by Hirata, Y. PubMed PubMed Citation Articles by Takeda, R. Articles by Hirata, Y.

Calcineurin is critical for sodium-induced neointimal formation in normotensive and hypertensive rats

¹Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo; ²Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki; and ³Department of Urology, Faculty of Medicine, and ⁴Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan

Submitted 10 January 2008 ; accepted in final form 25 April 2008

It is well known that excessive intake of sodium chloride (sodium) is a risk factor for cardiovascular disease because it raises blood pressure. However, sodium loading reportedly promotes cardiovascular disease independently of its effect on blood pressure. To examine the mechanisms by which sodium loading promotes vascular inflammation independently of its effect on blood pressure, we examined the role of calcineurin in sodium loading-induced vascular inflammation using a wire injury model of the rat femoral artery. Calcineurin mRNA expression in the wire-injured femoral artery was significantly higher in sodium-loaded normotensive rats, such as Wistar-Kyoto (WKY) rats, than that in control WKY rats. Neointimal formation was also significantly enhanced in sodium-loaded WKY rats compared with control WKY rats. Gene transfer of an adenovirus expressing a dominant negative mutant of calcineurin (AdCalAC92Q) significantly suppressed neointimal formation in sodium-loaded WKY rats to a level similar to that observed in control WKY rats. Calcineurin expression and neointimal formation were more significantly enhanced in hypertensive rats, such as spontaneously hypertensive rats (SHRs), than those in control WKY rats. AdCalAC92Q infection significantly suppressed neointimal formation in SHRs to a level similar to that observed in control WKY rats. These results suggest that sodium loading promotes neointimal formation, even in normotensive rats, and that hypertension further stimulates neointimal formation. These results also suggest that calcineurin plays a pivotal role in this process.

signal transduction; vasculature; inflammation; hypertension