Inheritance of salt-dependent hypertension in the inbred Dahl rat

The mode of inheritance of salt-dependent hypertension in the inbred Dahl salt-sensitive rat strain was examined by genetic crosses with the corresponding salt-resistant strain. The blood pressure responses to ingestion of a high NaCl (8%) diet defined three phenotypes: early onset (within 17 days) of systolic hypertension, defined as greater than or equal to 140 mm Hg, the parental salt-sensitive phenotype; late onset of systolic hypertension requiring 50 to 60 days in males and more than 200 days in females, characteristic of the F1 progeny; and normotension, less than 140 mm Hg, the parental salt-resistant phenotype. The frequencies of the phenotypes observed among 91 F2 progeny and 45 progeny of the backcross to parental salt-sensitive animals agree well with values predicted by a model in which two autosomal, unlinked, allelic loci, termed alpha and beta, determine the inheritance. For F2 male progeny, the predicted frequencies of early-onset hypertension, late-onset hypertension, and normotension are 0.1875, 0.5625, and 0.25, respectively, and the corresponding observed frequencies were 0.156, 0.50, and 0.34 (X2 = 0.48, P > .50). F1 progeny of reciprocal parental crosses were maintained on the 8% NaCl diet for 255 days. Male F1 rats developed systolic hypertension sooner than did females. From 60 to 200 days, the average blood pressure value within each group remained approximately stable; the male values exceeded those for females (P < .01); and the direction of the parental cross significantly influenced (P < .05) the levels in males and females, suggestive of genomic imprinting.