The frequent coincidence of hypertension and dyslipidemia suggests that related genetic factors might underlie these common risk factors for cardiovascular disease. To investigate whether quantitative trait loci (QTLs) regulating lipid levels map to chromosomes known to contain genes regulating blood pressure, we used a genome scanning approach to map QTLs influencing cholesterol and phospholipid phenotypes in a large set of recombinant inbred strains and in congenic strains derived from the spontaneously hypertensive rat and normotensive Brown-Norway (BN.Lx) rat fed normal and high cholesterol diets. QTLs regulating lipid phenotypes were mapped by scanning the genome with 534 genetic markers. A significant relationship ( P Ͻ 0.00006) was found between basal HDL2 cholesterol levels and the

The genes that determine the baseline hematocrit level in humans and experimental animals are unknown. The spontaneously hypertensive rat (SHR), the most widely used animal model of human essential hypertension, exhibits an increased hematocrit when compared with the normotensive Brown Norway (BN-Lx) strain (0.54 +/- 0.02 vs. 0.44 +/- 0.02, p < 0.01). Distribution of hematocrit values among recombinant inbred (RI) strains derived from SHR and BN-Lx progenitors was continuous, which suggests a polygenic mode of inheritance. The narrow heritability of the hematocrit was estimated to be 0.32. The Eno2 marker on Chromosome (Chr) 4 showed the strongest association (p < 0.0001) with the observed variability of hematocrit among RI strains. The erythropoietin (Epo) gene, originally reported to be syntenic with Eno2, has been mapped to Chr 12, thus excluding it as a potential candidate gene for the increased hematocrit in the SHR. The current linkage data extend homologies between rat, mouse, and human chromosomes.

To investigate whether molecular variation in the renin gene contributes to the greater blood pressure of spontaneously hypertensive rats (SHR) versus normotensive Brown Norway (BN) rats, we measured blood pressure in an SHR progenitor strain and an SHR congenic strain that are genetically identical except at the renin gene and an associated segment of chromosome 13 transferred from the BN strain. Backcross breeding and molecular selection at the renin locus were used to create the SHR congenic strain (designated SHR.BN-Ren) that carries the renin gene transferred from the normotensive BN strain. We found that transfer of the renin gene from the BN strain onto the genetic background of the SHR did not decrease blood pressure in rats fed either a normal or high-salt diet. In fact, the systolic blood pressures of the SHR congenic rats tended to be slightly greater than the systolic blood pressures of the SHR progenitor rats. However, the congenic strain exhibited lower serum high-density lipoprotein cholesterol, and greater levels of total cholesterol, very-low-density lipoprotein, and intermediate-density lipoprotein cholesterol during administration of a high-fat, high-cholesterol diet. These findings demonstrate that (1) under the environmental circumstances of the current study, the greater blood pressure of SHR versus BN rats cannot be explained by strain differences in the renin gene and (2) a quantitative trait locus affecting lipid metabolism exists on chromosome 13 within the transferred chromosome segment. The SHR.BN-Ren congenic strain may provide a useful new animal model for studying the interaction between high blood pressure and dyslipidemia in cardiovascular disease.