A genetic segregation analysis was performed to identify genes that cosegre
gate with arterial blood pressure traits reflective of salt sensitivity. A
population of 113 F2 male rats was derived from an intercross of inbred SS/
JrHsd/Mcw (Dahl salt-sensitive) and BN/SsN/Mcw (Brown Norway) rats. Rats we
re maintained on an 8% salt diet from the age of 9 to 13 wk, and arterial p
ressure was measured for 3 h daily during the 4th wk of high salt intake in
unanesthetized rats using implanted arterial catheters. At the end of the
3rd day of high-salt pressure recordings, the arterial pressure response to
salt depletion was determined 1.5 days following treatment with Lasix and
a low-sodium (0.4%) diet. A genome-wide scan using 265 polymorphic simple s
equence length polymorphism (SSLP) markers found that seven arterial pressu
re phenotypes determined at different times and circumstances, and represen
ting two distinct indexes of salt sensitivity, mapped to the same region of
rat chromosome 18. The trait of salt sensitivity was strongly influenced b
y the presence of SS alleles in this region of chromosome 18, and those rat
s which were homozygote SS/SS exhibited a significantly greater reduction o
f mean arterial pressure following sodium depletion (29 +/- 2 mmHg) than ho
mozygote BN/BN (17 +/- 3 mmHg) or heterozygotic (22 +/- 2 mmHg) rats. This
region of rat chromosome 18 corresponds to the long arm of human chromosome
5 and a region of human chromosome 18 that has been linked to hypertension
in humans. Given the unlikely chance of these different blood pressure tra
its mapping to the same region, we believe these data provide evidence that
this region of rat chromosome 18 plays an important role in salt-induced h
ypertension.