Screening for candidate genes involves in essential hypertension

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For the study of essential hypertension, spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) have proven to be valuable models. In the present study, we applied a fluorescent differential display method to mRNAs from aortae of SHR, SHRSP and their parental strain, Wistar Kyoto rats (WKY) towards identifying the genes involved in the development of the hypertension, and came across a gene which is consistently upregulated in the hypertensive rats. Nucleotide sequence determination of the corresponding cDNA revealed that the gene is the rat orthologue of cyr61. Northern blot analysis showed that cyr61 expression increases in SHR and SHRSP before the onset of hypertension, and is sustained thereafter at higher levels than in age-matched WKY. In situ hybridization analysis demonstrated that cyr61 is expressed strongly in smooth muscle cells in media, and faintly in fibroblasts in adventitia, of the hypertensive rat aorta, while in WKY the expression is only in fibroblasts. Fluorescent in situ hybridization mapped the cyr61 gene to rat chromosome 1p12-13, which has not been previously reported as a quantitative trait locus for blood pressure regulation. These results suggest that cyr61 is an additional factor which may be involved in the development of systemic hypertension.