Existence of Multiple Blood Pressure loci on Rat Chromosome 13 of the Dahl S Hypertensive Rat

Abstract

The aim of the present study was to identify the regions within Chr 13 involved in the development of salt-induced hypertension. We had previously reported an effect on salt-sensitive blood pressure and proteinuria, in a chromosome substitution strain for Chr 13. Consomic rats (SS-13BN) were backcrossed to Dahl SS (SS) rats, and the offspring intercrossed, to generate a population of 23 overlapping congenic rats for Chr 13. Blood pressure salt-sensitivity was determined after 2 weeks of high salt diet (8% NaCl) together with microalbuminuria. We found four discrete regions, ranging in size from 4.5 to 16 Mbp, each of which independently provided significant protection from salt-induced hypertension, reducing blood pressure sensitivity by 22–32 mmHg. Among the 23 congenic strains, several broadly overlapped with each other. When three of the “protective” regions were combined onto one broad congenic strain, no summation effect was seen between these regions, obtaining the same decrease in blood pressure as with each one independently, suggesting that these three regions act through the same final common pathway to lower blood pressure, through an epistatic interaction. Protection from salt-induced hypertension was more robust in female than in male rats in some of the congenic strains, suggesting a gender interaction with some of the genes determining blood pressure salt-sensitivity. Support: HL54998-09