Y-chromosome transfer induces changes in blood pressure and blood lipids in SHR

Previous studies with chromosome-Y consomic strains of spontaneously hypert ensive rats (SHR) and Wistar-Kyoto rats suggest that a quantitative trait l ocus for blood pressure regulation exists on chromosome Y. To test this hyp othesis in the SHR-Brown Norway (BN) model and to study the effects of chro mosome Y on lipid and carbohydrate metabolism, we produced a new consomic s train of SHR carrying the Y chromosome transferred from the BN rat. We foun d that replacing, the SHR Y chromosome with the BN Y chromosome resulted in significant decreases in systolic and diastolic blood pressures in the SHR .BN-Y consomic strain (P <0.05). To elicit possible dietary-induced variati on in lipid and glucose metabolism between the SHR progenitor and chromosom e-Y consomic strains, we fed rats a high-fructose diet for 15 days in addit ion to the normal diet. On the high-fructose diet, the SHR.BN-Y consomic ra ts exhibited significantly increased levels of serum triglycerides and decr eased levels of serum HDL cholesterol versus the SHR progenitor rats. Gluco se tolerance and insulin/glucose ratios, however, were similar in both stra ins on both normal and high-fructose diets. These findings provide direct e vidence that a gene or genes on chromosome Y contribute to the pathogenesis of spontaneous hypertension in the SHR-BN model. These results also indica te that transfer of the Y chromosome from the BN rat onto the SHR backgroun d exacerbates dietary-induced dyslipidemia in SHR. Thus, genetic variation in genes on the Y chromosome may contribute to variation in blood pressure and lipid levels and may influence the risk for cardiovascular disease.