Genetic effects of blood pressure quantitative trait loci on hypertension-related organ damage: evaluation using multiple congenic strains.

On rat chromosome 1, quantitative trait loci (QTLs) for susceptibility to hypertension-related renal diseases and cerebral stroke are identified in a cluster, some of which have been previously claimed to be independent of hypertension. In this study, we therefore attempted to excise genomic regions contributing to salt-induced renal damage and cerebral stroke using five congenic rats for blood pressure QTL on chromosome 1, which were constructed between SHRSP/Izm and WKY/Izm. Male rats from the five strains with different congenic segments of chromosome 1 were used in these experiments. All congenic strains harbored a fragment derived from Wistar-Kyoto (WKY) rats in the background of stroke-prone spontaneously hypertensive rat (SHRSP). Salt-loading was initiated using 1% NaCl in the drinking water when the rats were 12 week old. Histopathological evaluation of glomerulosclerosis, measurement of urinary albumin excretion, cumulative incidence of cerebral stroke and measurement of blood pressure were performed after 2 to 5 weeks of salt-loading. Substantial differences in the severity of renal damage and the incidence of cerebral stroke were observed among the five congenic strains. The cumulative incidence of cerebral stroke correlated well with the basal blood pressures of the congenic strains measured before salt-loading (Pearson's r=0.97, p=0.006), suggesting a substantial influence of blood pressure on the incidence of stroke. In contrast, the severity of glomerulosclerosis did not have a significant correlation with basal blood pressure. These results suggest that a gene (or genes) contributing to salt-induced renal damage is located in this chromosomal region.