Nuclear Medicine Technology and Other Health Applications
Interrelationsip between Genetic and Environmental Factors
Projece Title: in Clinical and Experimental Hypertension
16.
Technical Progress in FY 1973:
RX-01-03-(b)
(Cont'd.)
Studies on glomerular filtration rate with C-14 inulin and on renal
blood flow with para-amino-hippurate were performed on R and §S rats with
renal homografts from either strain; as compared with similar studies on
appropriate controls, normal renal function was observed in the animals
with homografts for up to ten months--the Longest period studied.
‘Studies on corticosteroid production and genetic effects on blood
pressure in the salt susceptible and salt resistant strains of rats
were completed in collaboration with Dr. John Rapp.
Classical quantitative
genetic techniques suggest that the genetic component of blood pressure in
these strains is controlled by relatively few genetic loci,
order of 2-4.
i.e., on the
One such locus with 2 alleles inherited by co-dominance was
identified which controls adrenal output of 18-hydroxy-deoxycorticdésterone
(180H-DOC), a hypertensinogenic mineralocorticoid,
This locus accounts
for approximately 16% of the blood pressure difference between S and R
strains with the remaining 84% due to other, unidentified genes.
Studies on the influence of dietary potassium and Na/K molar ratios
on the development of salt hypertension were completed, Among genetically
hypertension-prone rats, dietary sodium (chloride) was demonstrably hypertensinogenic and potassium (chloride) antihypertensinogenic.
On diets
containing the same NaCl but different KCl concentrations, mean blood
pressure was greater in rats receiving less dietary potassium,
i.e., diets
with a higher Na/K molar ratio. On diets with different absolute concentrations of NaCl and KCl, but the same Na/K molar ratios, rats on the
higher absolute NaCl intakes had the higher blood pressures,
On diets with
different absolute concentrations of NaCl and KCL, and different Na/K molar
ratios, a group on a lower absolute NaCl intake but with a higher Na/K
ratio could have more hypertension than a group on a higher absolute NaCl
intake but with a lower Na/K ratio, At equivalent molar ratios, the
respective effects of these two ions on blood pressure were dominated by
that of sodium.
It was concluded that the dietary Na’K molar ratio can
be an important determinant for the severity, or even development, of
salt-induced hypertension,
The mechanism of the moderating effect of
potassium on sodium-induced hypertension is unclear,
A genetic study involving a cross between the BNL § rats and the
Japanege spontaneously hypertensive rats (SHR) was initiated in an effort:
a) to @@termine what genes are shared in common, and b) to improve the
est imal of the number of genes
involved
in the R and S$ strains.
F, rats
off and on NaCl are being bred for backcross and F9 generations and the
BP response observed,
Early study of SHR on high and low NaCl diets
shows that SHR and Fj rats on NaCl develop hypertension more rapidly and
die earlier than comparable animals on low NaCl.
Adrenal transplant studies were reactivated.
About 50 successful
transplants were performed (confirmed at autopsy after death).
Inspection
of the data suggests chat. no major change in the usual evolution of blood
(See Continuation Sheet)
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