EFFECTS OF CHRONIC EXCESS SALT INGESTION

Abstract

Two strains of rat have been developed by selective breeding: one strain (R rats) is resistant to salt hypertension, the other strain (S rats) is highly susceptible. The inheritance of these traits has been explored in the first (F1) and second (F2) generation of crossbred rats and in backcrosses between parent and first filial (F1 x R, F1 x S) generations. Male F1 rats had an average blood pressure close to the mid-parental (R and S) values, and the average of F2 males was equivalent to that of F1. Male offspring of F1 with R, or F1 with S also showed averages close to the respective mid-parental values. Female offspring showed deviations from this linear relationship, indicating a significant dominance in the female for the genes of normal blood pressure. A model of two autosomal, nonlinked diallelic loci, with a dominance deviation at one locus in the female, gave predictions with a reasonable agreement to the observed values. The same model also appeared compatible with human data if we assume a gene frequency of 0.13 for the hypertensinogenic allele on both loci. Random fluctuations in blood pressure, and incomplete homogeneity of parental strains permit several alternative models. The major conclusions are: that more than one locus is needed to explain the findings though as few as two loci may possibly suffice; the allelic effect seems additive in males, but there is a sex-determined influence on the expression in females; there is no consistent evidence for sex-linked inheritance. Furthermore, this model developed from the study of rats may provide a framework for analysis of human data.