Cosegregation of the endothelin-3 locus with blood pressure and relative heart weight in inbred Dahl rats.

Cicila GT, Rapp JP, Bloch KD, Kurtz TW, Pravenec M, Kren V, Hong CC, Quertermous T, Ng SC
J Hypertens. 1994 12 (6): 643-51

PMID: 7963489

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.

CONCLUSION - 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.

MeSH Terms (10)

Animals Blood Pressure Chromosome Mapping Endothelins Heart Hypertension Organ Size Polymorphism, Restriction Fragment Length Rats Rats, Inbred Strains

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