In man, hereditary factors are recognized as essential in the etiology of hypertension. The genetic expression is, however, difficult to assess because it is not known how many genes are involved, how they interact with one another and with environmental factors, or by what mechanisms they exert their influence.In rats, the genetic influence on blood pressure regulation is definitely established. If similar factors operate in humans, rat colonies may provide prototypes of heredity and blood pressure regulation for the study of human health and disease. Work at this laboratory demonstrated in 1962 that the development of salt-induced hypertension strongly depended upon the genetic backgroand of the rats used (1, 2). By selective breeding, two colonies were derived from a single Sprague-Dawley strain. In one colony the rats rapidly developed hypertension on the same salt (NaC1) intake to which members of the other colony were resistant. Later we confirmed these differences with other techniques generally used to induce experimental hypertension. These techniques included: DOCA plus NaC1, unilateral renal artery compression without NaC1, cortisone, adrenal regeneration, and uninephrectomy without NaC1 (3-5). If these experimental models have relevance to man, then several forms of human hypertension would also require for their emergence an appropriate genetic substratum which depends upon environmental determinants for its expression (4).In the present work, which extended over a six year period, we have explored the mode of inheritance of hypertension in these two strains of rats. Approximately 2000 animals were studied in an effort to determine the number of genes involved. The data indicated that regulation of blood pressure is multigenic; the probable number of genes was calculated to be from two to four. The simplest model compatible with our data consists of two nonlinked, autosomal, diallelic loci with a sex-modified expression of the genes at one locus.
Materials and MethodsRats were housed three to a cage in air-conditioned rooms, lighted for 10 hr each day. The food pellets were made to order and contained a total of 8% NaC1 (w/w). Pellets and
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