[Importance of chromosome 17 in genetically hypertensive rats of the Lyon strain (LH): study of a consomic strain]

Abstract

Genetically hypertensive rats of the Lyon strain (LH) associate high blood pressure (BP), exaggerated salt-sensitivity, and a metabolic syndrome made of overweight together with increased plasma lipids and insulin/glucose ratio. A genetic mapping study in a large population of F2 rats derived from a cross between hypertensive (LH) and normotensive rats (LN) showed the existence, on chromosome 17, of two clusters of Quantitative Traits Loci (QTLs). The first one was associated to morphological parameters whereas the second influenced blood pressure and plasma lipids level. In order to determine the functional importance of this QTLs, we generated a consomic strain LH-17BN in which the LH chromosome 17 has been fully substituted by a normotensive Brown Norway (BN) one. These LH-17BN, as well as LH and BN male rats of the parental strain were phenotyped. This included radio telemetric measurement of BP during normal and elevated salt intake (1% and then 2% in the drinking water) as well as the determination of morphological, metabolic (triglycerides, cholesterol) and renal (creatinine clearance, proteinuria) parameters. LH-17BN, compared to LH rats, exhibited significant decreases in body weight and blood pressure. Renal functions are improved (decreased of proteinuria). Finally, plasma triglycerides were reduced and reach the level observed in BN rats. In conclusion, the present work demonstrates that, in our model, chromosome 17 contains genes which influence morphology, blood pressure, renal function, and lipid metabolism. Interestingly, chromosome 17 almost completely explains the spontaneous hypertriglyceridemia observed in Lyon Hypertensive rats.