SEPARATE SEX-INFLUENCED AND GENETIC COMPONENTS IN SPONTANEOUSLY HYPERTENSIVE RAT HYPERTENSION

Previous results from our laboratory indicated two major genetic components of spontaneously hypertensive rat (SHR) hypertension, an autosomal component and a Y chromosome component. Two new substrains, SHR/a and SHR/y, were developed using a series of backcrosses to isolate each of these components. The SHR/a substrain has the autosomal loci and X chromosome from the SHR strain and the Y chromosome from the Wistar-Kyoto (WKY) rat strain. The SHR/y substrain has only the Y chromosome from the SHR and autosomal loci and X chromosome from the WKY strain. Throughout these breeding programs parents were chosen at random without selection for blood pressure. Males of both substrains maintained blood pressures over 180 mm Hg. Comparisons of blood pressure in these new substrains with the original parental strains can be used to determine the relative proportions of each genetic component in hypertension. The Y chromosome component contributes 34 mm Hg, which is the difference between SHR/y male and WKY male blood pressure. The total autosomal component contributes 46 mm Hg, which is the difference between SHR/a male and WKY male blood pressure. The autosomal component is a sex-influenced trait; males in the SHR/a strain have significantly higher pressures than SHR/a females. Of the 46 mm Hg estimated for the autosomal component, 41 mm Hg is the result of these loci interacting with male phenotypic sex. This sex-influenced component is separate and distinct from the Y chromosome component.