Methods Production of Congenic Strains and Blood Pressure Measurements

Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The stroke-prone spontaneously hypertensive rat (SHRSP) is a model of human essential hypertension, and a number of reproducible blood pressure regulation quantitative trait loci have been found to map to rat chromosome 2. The SP.WKYGla2c* congenic strain was produced by introgressing a region of rat chromosome 2 from the normotensive Wistar Kyoto (WKY) strain into the genetic background of the SHRSP. Systolic and diastolic blood pressures were significantly reduced in the SP.WKYGla2c* compared with the SHRSP parental strain (198/134 6.1/3.3 versus 172/120 3.8/3.4 mm Hg; F 15.8/8.1, P 0.0009/0.013). Genome-wide microarray expression profiling was undertaken to identify differentially expressed genes among the parental SHRSP, WKY, and congenic strain. We identified a significant reduction in expression of glutathione S-transferase -type 2, a gene involved in the defense against oxidative stress. Quantitative reverse transcription–polymerase chain reaction relative to a -actin standard confirmed the microarray results with SHRSP mRNA at 8.56 10 4 1.6 10 4 compared with SP.WKYGla2c* 3.67 10 3 2.8 10 4 (95% CI 3.9 10 3 to 1.8 10 ; P 0.0034) and WKY 4.03 10 3 5.1 10 ; (95% CI 5.4 10 3 to 8.9 10 ; P 0.027). We also identified regions of conserved synteny, each containing the Gstm2 gene, on mouse chromosome 3 and human chromosome 1. (Hypertension. 2003;41[part 2]:847-853.)