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Project Title:
16,
Nuclear Medicine Technology and Other Health Applications
Interrelationship between Genetic and Environmental Factors
in Clinical and Experimental Hypertension
Technical Progress
diet,
in FY 1973:
(Cont'd.)
RX-01-03-(b)
If successful ome could study the interactions of hypertensino-and-
atherogenic influences experimentally in a fashion never before possible.
After 5-6 generations of inbreeding, 2 substrains from R and S strains are emerging with trends towards low and high plasma cholesterol.
Exceptions
appear,
however,
indicating that multiple genes are involved and that it
may take longer to separate the substrains than anticipated,
There is evidence that some human hypertensives fail to suppress
aldosterone adequately in response to increased salt intake resulting in
inappropriately high aldosterone levels for such salt intakes, Aldosterone
production and zona glomerulosa size were studied in the S and R rats in
relation to salt intake in collaboration with Dr, John Rapp.
With either
in vitro or in vivo systems S rats suppressed aldosterone production in
response to salt as much or more than R animals, Zona glomerulosa mass was
not different between S and R rats on various salt intakes,
It was concluded
that S rats are able to normally suppress aldosterone in response to salt
in spite of their genetically controlled increment in adrenal 18-hydroxylase
activity reported previously.
The study on radiation-genetic interaction in experimental hypertension
is dormant,
The initial study was completed but incompletely analyzed:
the
absence of Dr. Knudsen, effectively since early Spring 1972, has slowed this
work,
Circumstantial evidence suggests that "overeating™ promotes and
“undereating" retards manifestations of hypertension, atherosclerosis,
diabetes, gout, and obesity,
Each may present varying degrees of hypertension, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, hyper-
lacticacidemia, glucose intolerance, and insulin insensitivity, Patients
with one of the diseases frequently develop one or more of the others.
Although the mode of inheritance is not known the genetic factors are
probably multi-factorial.
In benign forms the diseases are usually found
in middle or old age whereas malignant forms may occur in youth.
It is
proposed that the association among the five diseases above indicates that
they share some genetically determined biochemical defects in which the
character of the clinical manifestations will be influenced by the nature
of the input from the environment, i.e., im a sense, the kind of "overeating".
tole
where
We 68 hypertensive patients 25% had a strongly abnormal glucose
@ curve, 25% had a borderline abnormal response, and 50% were normal,
“non-hypertensive controls were 0, 25, and 75% respectively.
These
differences were significant after correction for age, weight, and sex,
Blood insulin levels after a glucose load determined by immunoassay have
been reported by another group to be abnormally high in hypertensives,
In
the 68 BNL hypertensives 35, 43, and 22% had "high", "borderline", and
(See Continuation Sheet)
1119210
RX-52