Unlike human hypertension, blood pressure in a hereditary hypertensive rat strain shows no linkage to the angiotensinogen locus.
Recently, evidence has been presented for genetic linkage between the angiotensinogen gene and primary hypertension in humans. In the present study we examined whether a similar linkage between blood pressure and the angiotensinogen gene locus can be demonstrated in a widely used animal model of primary hypertension, the stroke-prone spontaneously hypertensive rat (Heidelberg colony, SHRSPHD). In 115 F2 hybrids bred from SHRSPHD and a normotensive reference strain, the Wistar-KyotoHD (WKYHD) rat, systolic and diastolic blood pressures and heart rate were determined by indwelling arterial catheters in the presence and absence of dietary sodium loading. In addition, left and right ventricular heart weight was measured. Using a newly developed polymorphic marker assay for the angiotensinogen gene based on polymerase chain reaction amplification of an exon 2 fragment and subsequent restriction endonuclease digestion, we performed a cosegregation study in this cohort. No evidence for cosegregation between the angiotensinogen gene locus and blood pressure or any other phenotypic parameter assessed was found. Although the SHRSP serves as a valuable model of hypertension, our data emphasize that disease-relevant genetic loci in humans and rats cannot be assumed to coincide.
Hübner
N
N
Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
Kreutz
R
R
Takahashi
S
S
Ganten
D
D
Lindpaintner
K
K
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D002874:Chromosome Mapping; D008040:Genetic Linkage; D005838:Genotype; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics* / Q000502:physiology*
D015335:Molecular Probes; D000808:Angiotensinogen