Y-chromosome transfer induces changes in blood pressure and blood lipids in SHR.
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.
Kren
V
V
Institute of Biology and Medical Genetics, First Medical Faculty, Charles University, Prague, Czech Republic.
Qi
N
N
Krenova
D
D
Zidek
V
V
Sladká
M
M
Jáchymová
M
M
Míková
B
B
Horky
K
K
Bonne
A
A
Van Lith
H A
HA
Van Zutphen
B F
BF
Lau
Y F
YF
Pravenec
M
M
St  Lezin
E
E
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000209:etiology; D008076:Cholesterol, HDL / Q000097:blood; D004032:Diet; D005632:Fructose / Q000008:administration & dosage; D005838:Genotype; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D014998:Y Chromosome
D001786:Blood Glucose; D008076:Cholesterol, HDL; D007328:Insulin; D008055:Lipids; D014280:Triglycerides; D005632:Fructose