Aging and salt-loading modulate blood pressure QTLs in rats

To evaluate the effects of nongenetic factors, aging, and salt-loading on t he quantitative trait loci (QTLs) for blood pressure (BP), we conducted a g enome-wide linkage analysis using multiple sets of BP measurements in 125 m ale F2 generation cross derived from stroke-prone spontaneously hypertensiv e rats and normotensive Wistar-Kyoto rats. The experiment was arranged in t wo stages. In the first stage, corresponding to the developing period of th e mts, BP was measured repeatedly without loading of salt; this continued u ntil the rats were 5 months of age. In the second stage, after the baseline BP leveled off, 1% salt water was given to the rats and BP was monitored f or the subsequent 7 months. Genome scanning was performed using 201 markers , In the developing period, three QTLs were identified on chromosomes 1, 3, and 4 (logarithmic odds [LOD] scores of 5.6, 3.1, and 3.5 respectively), w hich had peaks at 8 or 10 weeks of age. In the latter salt-loading stage, Q TLs for BP were detected on chromosomes 1 and 10 (LOD scores 4.6 and 4.5, r espectively). When the BP increase during salt-loading was analyzed as a ph enotype, however, only the region on chromosome 10 showed linkage at a sugg estive level (LOD score 3.2). The present study provides experimental evide nce that QTLs for BP could be modulated by nongenetic factors, such as agin g and salt-loading. (C) 1999 American Journal of Hypertension, Ltd.