Cosegregation of the endothelin-3 locus with blood pressure and relative heart weight in inbred Dahl rats.
OBJECTIVE
To determine whether the endothelin-1 or endothelin-3 genes are genetically linked with blood pressure and relative heart weight in segregating rat populations, in the context of an elevated dietary sodium chloride intake.


METHODS
Endothelin-1 and endothelin-3 genotypes of rats in segregating populations, derived from crosses of Dahl salt-sensitive (SS/Jr) rats with contrasting inbred strains, including Lewis rats, spontaneously hypertensive rats and Dahl salt-resistant (SR/Jr) rats, were determined using restriction fragment length polymorphisms. Segregating populations were fed a high (8%)-sodium chloride diet. Linkage of genotype with blood pressure or relative heart weight was determined by analysis of variance. Chromosomal location of the rat endothelin-3 gene was determined by genotyping a panel of recombinant inbred strains.


RESULTS
Two alleles for the endothelin-1 gene and three alleles for the endothelin-3 gene were identified. The endothelin-1 locus did not cosegregate with blood pressure or relative heart weight. The endothelin-3 locus cosegregated with blood pressure and relative heart weight in an SS/Jr x F1 (SS/Jr x SR/Jr) population, but not in populations containing a higher percentage of genes from the SR/Jr strain. The endothelin-3 and seminal vesicle protein-1 loci were linked and located on rat chromosome 3.


CONCLUSIONS
The endothelin-3 gene is, or is linked to, a locus on chromosome 3 that regulates blood pressure and relative heart weight in inbred Dahl rats, and these effects were strongly dependent on the genetic background.
Cicila
G T
GT
Cosmopolitan International Diabetes Center, University of Missouri, Columbia 65212.
Rapp
J P
JP
Bloch
K D
KD
Kurtz
T W
TW
Pravenec
M
M
Kren
V
V
Hong
C C
CC
Quertermous
T
T
Ng
S C
SC
D000818:Animals; D001794:Blood Pressure; D002874:Chromosome Mapping; D016232:Endothelins / Q000235:genetics*; D006321:Heart / Q000033:anatomy & histology*; D006973:Hypertension / Q000235:genetics*; D009929:Organ Size; D012150:Polymorphism, Restriction Fragment Length; D051381:Rats; D011919:Rats, Inbred Strains
D016232:Endothelins