A paradigm for identification of primary genetic causes of hypertension in rats.

A paradigm is developed for identifying the genes (and the biochemical-physiological traits for which the genes code) that cause differences in blood pressure in inbred strains of rats. A biochemical-physiological trait which meets the following four criteria is one which can reasonably be accepted as causing genetic differences in blood pressure: 1) a difference in a biochemical or physiological trait between two strains must be demonstrated; 2) the trait must be shown to follow Mendelian inheritance; 3) the genes identified in criterion 2 must co-segregate with an increment in blood pressure which is significantly different from zero; and 4) there must be some logical biochemical and/or physiological link between the trait and blood pressure. Traits which do not show discrete phenotypes following Mendelian inheritance may correlate with blood pressure in segregating populations. In this case no rigorous cause and effect genetic argument is possible because such correlations could arise from complex primary genetic causes or as secondary effects of blood pressure on the biochemical-physiological trait.