Submitted on September 20, 2004
Accepted on March 23, 2005
Differential Renal Gene Expression in Pre-hypertensive and Hypertensive Spontaneously Hypertensive Rats
J M Seubert1, F Xu2, J P Graves1, J B Collins3, S O Sieber3, R S Paules3, D L Kroetz2, and D C Zeldin1*
1 Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
2 Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco, CA, USA
3 Microarray Group, NCT, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
* To whom correspondence should be addressed. E-mail: zeldin{at}niehs.nih.gov.
Development of hypertension stems from both environmental and genetic
factors wherein the kidney plays a central role. Spontaneously hypertensive rats
(SHR) and the non-hypertensive 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 pre-hypertensive stage (3 weeks
of age) and hypertensive stage (9 weeks of age). Additionally, age-related
changes in gene expression patterns were examined from 3 to 9 weeks 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 NIEHS Rat v2.0 Chip which contains approximately 6700 genes.
Twenty two genes were found to be differentially expressed between SHR and
WKY at 3 weeks of age, and 104 genes were differentially expressed at 9 weeks
of age. Soluble epoxide hydrolase (Ephx2) was found to be significantly up-regulated
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 weeks 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.
