Genetics of Blood Pressure and Associated Phenotypes in the Lyon Rat

Abstract

The Lyon model of genetic hypertension is made of 3 simultaneously selected strains, one hypertensive (LH) one normotensive (LN) and one with low blood pressure (LL). Since LN and LL rats exhibit the same blood pressure (BP) LH rats can be compared to 2 genetically pure and different strains of control animals. This proved to be useful for the interpretation of the data of molecular genetic studies, eg: since the renin gene was polymorphic between LH and LN but not between LH and LL rats it could be suggested that the reported linkage of renin gene polymorphism and high BP in F2 hybrids may involve another closely located gene. LH rats associate to high BP spontaneous increases in body weight, plasma cholesterol, fibrinogen and hematocrit. During the phenotyping of F1 and F2 hybrids from a LH × LN cross and of back-crosses to LH rats it was observed that ali these phenotypes were recessive, except the large body weight of LH rats which was dominant and, thus, unrelated to BP. On the contrary, BP was significantly related to plasma cholesterol in both F2 and back-cross rats and, in this latter cohort, plasma cholesterol correlated also with fibrinogen and hematocrit levels. Therefore, the study of the Lyon rat may be useful not only to determine the genes involved in hypertension but also those which contribute to other cardiovascular risk factors such as elevated fibrinogen and hematocrit.