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Am J Physiol Renal Physiol 289: F552-F561, 2005. First published March 29, 2005; doi:10.1152/ajprenal.00354.2004
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Differential renal gene expression in prehypertensive and hypertensive spontaneously hypertensive rats

J. M. Seubert,1 F. Xu,2 J. P. Graves,1 J. B. Collins,3 S. O. Sieber,3 R. S. Paules,3 D. L. Kroetz,2 and D. C. Zeldin1

1Division of Intramural Research and 3Microarray Group, National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina; and 2Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco, California

Submitted 20 September 2004 ; accepted in final form 23 March 2005

Development of hypertension stems from both environmental and genetic factors wherein the kidney plays a central role. Spontaneously hypertensive rats (SHR) and the nonhypertensive Wistar-Kyoto (WKY) controls are widely used as a model for studying hypertension. The present study examined the renal gene expression profiles between SHR and WKY at a prehypertensive stage (3 wk of age) and hypertensive stage (9 wk of age). Additionally, age-related changes in gene expression patterns were examined from 3 to 9 wk in both WKY and SHR. Five to six individual kidney samples of the same experimental group were pooled together, and quadruplicate hybridizations were performed using the National Institute of Environmental Health Sciences Rat version 2.0 Chip, which contains ~6,700 genes. Twenty two genes were found to be differentially expressed between SHR and WKY at 3 wk of age, and 104 genes were differentially expressed at 9 wk of age. Soluble epoxide hydrolase (Ephx2) was found to be significantly upregulated in SHR at both time points and was the predominant outlier. Conversely, elastase 1 (Ela1) was found to be the predominant gene downregulated in SHR at both time points. Analysis of profiles at 3 vs. 9 wk of age identified 508 differentially expressed genes in WKY rats. In contrast, only 211 genes were found to be differentially expressed during this time period in SHR. The altered gene expression patterns observed in the age-related analysis suggested significant differences in the vascular extracellular matrix system between SHR and WKY kidney. Together, our data highlight the complexity of hypertension and the numerous genes involved in and affected by this condition.

soluble epoxide hydrolase; hypertension; arachidonic acid; elastase; real-time polymerase chain reaction


Address for reprint requests and other correspondence: D. C. Zeldin, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Bldg. 101, D236, Research Triangle Park, NC 27709 (e-mail: zeldin{at}niehs.nih.gov)






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