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 genotyp es of rats in segregating populations, derived from crosses of Dahl sa lt-sensitive (SS/Jr) rats with contrasting inbred strains, including L ewis rats, spontaneously hypertensive rats and Dahl salt-resistant (SR /Jr) rats, were determined using restriction fragment length polymorph isms. Segregating populations were fed a high (8%)-sodium chloride die t. Linkage of genotype with blood pressure or relative heart weight wa s 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 thr ee alleles for the endothelin-3 gene were identified. The endothelin-1 locus did not cosegregate with blood pressure or relative heart weigh t. The endothelin-3 locus cosegregated with blood pressure and relativ e heart weight in an SS/JrxF(1) (SS/JrxSR/Jr) population, but not in p opulations containing a higher percentage of genes from the SR/Jr stra in. The endothelin-3 and seminal vesicle protein-1 loci were linked an d located on rat chromosome 3. Conclusion: The endothelin-3 gene is, o r 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.