The alpha1 Na,K-ATPase gene is a susceptibility hypertension gene in the Dahl salt-sensitiveHSD rat.
Despite the prevalence of essential hypertension, its underlying genetic basis has not been elucidated due to the complexities of its determinants. To identify a hypertension susceptibility gene, we used an approach that integrates molecular, transgenic, and genetic analysis using Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats ascertained for genotype and phenotype. To determine the role of the Dahl S Q276L alpha1 Na,K-ATPase gene variant, we developed transgenic Dahl S rats bearing the Dahl R wild-type (wt) alpha1 Na, K-ATPase cDNA directed by the cognate wt promoter region, Tg[wtalpha1]. Transgenic Dahl S rats exhibited less salt-sensitive hypertension, less hypertensive renal disease, and longer life span when compared with non-transgenic Dahl S controls. Total chromosome 2 linkage analysis of F2(SxR) male rats detects cosegregation of the alpha1 Na,K-ATPase locus with salt-sensitive hypertension. These data support the alpha1 Na,K-ATPase gene as a susceptibility gene for salt-sensitive hypertension in the Dahl S rat model, and provide the basis for the study of the alpha1 Na,K-ATPase locus in human hypertension.
Herrera
V L
VL
Whitaker Cardiovascular Institute, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.vherrera@bu.edu
Xie
H X
HX
Lopez
L V
LV
Schork
N J
NJ
Ruiz-Opazo
N
N
D000818:Animals; D030801:Animals, Genetically Modified; D001795:Blood Pressure Determination; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003911:Dextrans / Q000494:pharmacology*; D004198:Disease Susceptibility; D004351:Drug Resistance; D008040:Genetic Linkage; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006973:Hypertension / Q000235:genetics*; D006977:Hypertension, Renal / Q000473:pathology; D010641:Phenotype; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D016019:Survival Analysis
D003911:Dextrans; C104375:hypertonic saline-dextran solution; D012965:Sodium Chloride; D000254:Sodium-Potassium-Exchanging ATPase