Y-Chromosome Transfer Induces Changes in Blood Pressure and Blood Lipids in SHR

Abstract

Abstract-Previous studies with chromosome-Y consomic strains of spontaneously hypertensive rats (SHR) andWistar-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 (PϽ0.05). 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.

Effects of the Y Chromosome on Cardiovascular Risk Factors in Japanese Men

“…Results based on the chromosome Y consomic strains derived from SHR and WKY rats have suggested the possible effect of Y chromosome on determination of BP (8)(9)(10)(11). It can be speculated that sexual dimorphism in cardiovascular risk can be partly explained by the effect of the Y chromosome, and polymorphisms within the male specific non-recombining region of the Y chromosome are linked to increased cardiovascular risk in men.…”

“…Analyses of the Y chromosome consomic strains derived from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) revealed the possible effect of the Y chromosome on determination of blood pressure (BP), with an SHR Y chromosome in a WKY genetic background exerting the BP-elevating effect (8)(9)(10). Similarly, replacement of the SHR Y chromosome with that of Brown Norway rats has been associated with significant reduction in both SBP and DBP (11).…”

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

“…Most of these studies examined the impact of a high-fat/high-cholesterol diet on serum lipids. 29,39,40 To the best of our knowledge, however, the effect of HFD on adiposity and BP has not been compared between SHR and BN. It has been demonstrated, though, that SHR compared with other normotensive strains, namely, Wistar-Kyoto or Sprague-Dawley rats, are resistant to weight gain in response to HFD feeding; they either do not increase BW 41 or increase it less than does the normotensive strain.…”

The Y Chromosome Effect on Blood Pressure in Two European Populations

“…2 Extensive data from rodent models indicate a significant association between the Y chromosome and BP. [3][4][5][6][7][8] Moreover, human studies have shown that a hypertensive father but not a mother affects BP in normotensive male offspring. 9 Recently, Ellis et al 10 reported an association between an increased risk of elevated diastolic blood pressure (DBP) and a biallelic polymorphism on the NRY region of the Y chromosome in 409 subjects recruited from the general population in Victoria, Australia.…”