Kren V, Qi N, Krenova D, Zidek V, Sladká M, Jáchymová M, Míková B, Horky K, Bonne A, Van Lith H A, Van Zutphen B F, Lau Y F, Pravenec M, St Lezin E
Institute of Biology and Medical Genetics, First Medical Faculty, Charles University, Prague, Czech Republic.
Hypertension. 2001 Apr;37(4):1147-52. doi: 10.1161/01.hyp.37.4.1147.
Previous studies with chromosome-Y consomic strains of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats suggest that a quantitative trait locus for blood pressure regulation exists on chromosome Y. To test this hypothesis in the SHR-Brown Norway (BN) model and to study the effects of chromosome Y on lipid and carbohydrate metabolism, we produced a new consomic strain of SHR carrying the Y chromosome transferred from the BN rat. We found 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 variation in lipid and glucose metabolism between the SHR progenitor and chromosome-Y consomic strains, we fed rats a high-fructose diet for 15 days in addition to the normal diet. On the high-fructose diet, the SHR.BN-Y consomic rats exhibited significantly increased levels of serum triglycerides and decreased levels of serum HDL cholesterol versus the SHR progenitor rats. Glucose tolerance and insulin/glucose ratios, however, were similar in both strains on both normal and high-fructose diets. These findings provide direct evidence that a gene or genes on chromosome Y contribute to the pathogenesis of spontaneous hypertension in the SHR-BN model. These results also indicate that transfer of the Y chromosome from the BN rat onto the SHR background 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.
先前对自发性高血压大鼠（SHR）和Wistar-Kyoto大鼠的Y染色体代换系的研究表明，Y染色体上存在一个调节血压的数量性状基因座。为了在SHR-布朗挪威（BN）模型中验证这一假设，并研究Y染色体对脂质和碳水化合物代谢的影响，我们培育了一种新的SHR代换系，其携带从BN大鼠转移而来的Y染色体。我们发现，用BN大鼠的Y染色体替换SHR的Y染色体后，SHR.BN-Y代换系的收缩压和舒张压显著降低（P<0.05）。为了引发SHR亲代和Y染色体代换系之间可能由饮食诱导的脂质和葡萄糖代谢差异，我们在正常饮食之外，给大鼠喂食高果糖饮食15天。在高果糖饮食条件下，与SHR亲代大鼠相比，SHR.BN-Y代换系大鼠的血清甘油三酯水平显著升高，血清高密度脂蛋白胆固醇水平降低。然而，在正常饮食和高果糖饮食条件下，两个品系的葡萄糖耐量和胰岛素/葡萄糖比值相似。这些发现提供了直接证据，表明Y染色体上的一个或多个基因促成了SHR-BN模型中自发性高血压的发病机制。这些结果还表明，将BN大鼠的Y染色体转移到SHR背景上会加剧SHR饮食诱导的血脂异常。因此，Y染色体上基因的遗传变异可能导致血压和血脂水平的差异，并可能影响心血管疾病的风险。
