Abstract
1. The acute fibrinoid necrosis of visceral arterioles
which occurs in the malignant phase of hypertension is generally
attributed to the critical rise in blood
pressure which takes
place in this condition. Experimental evidence, obtained in the
rat with deoxycortone hypertension, led to the hypothesis that
early in the development of the hypertension a change occurred
in the internal environment of the smooth muscle cell which
might predispose the cell to necrosis.
2. It was suggested that this alteration might be, or
could be attributable to, a disturbance of the energy production
by metabolism in the cell. A study of selected enzymes in the
arterioles of rats in the early phase of deoxycortone hypertension was therefore undertaken. As
energy production in cardiac
muscle
may also be disturbed when raised blood pressure is
maintained, enzymes in this muscle were also studied.
3. The techniques chosen for enzyme assays were those
which could subsequently be adapted to the study of isolated
arteriolar smooth muscle cells. Methods were developed for the
preparation of freeze-dried vascular tissue and for the assay of
alkaline phosphatase, glucose-6-phosphate dehydrogenase, lactate
dehydrogenase and malate dehydrogenase in microgram quantities
of this material. The localisation of the
enzymes was also
studied by qualitative histochemical methods.
4. Hypertension was initiated in male, albino, Wistar
rats by implanting deoxycortone acetate subcutaneously in
uninephrectomised,salt-loaded animals. Control groups of
uninephrectomised rats, salt-loaded rats and normal animals were
maintained under identical conditions.
5. A significant decrease in alkaline phosphatase activity
and a significant increase in glucose-6-phosphate dehydrogenase
activity were found in the cardiac tissue of deoxycortonetreated rats after one week: the systolic blood pressure had
risen significantly in these animals. Changes of a similar
size were found in the activity of these two enzymes in the
cardiac tissue of control uninephrectomised and salt-loaded
animals: a slight but statistically significant increase in
blood
pressure occurred in these groups.
No differences were found in the mean values of the
activities of lactate dehydrogenase or malate dehydrogenase in
heart tissue from the four groups.of rats.
6. The different relationships observed between cardiac
alkaline phosphatase activity and the blood pressure in the
individual animals of the treated
groups suggested that the
enzyme value showed a trend of returning to normal in these
animals in which raised blood
pressure was accompanied by
compensatory renal hyperplasia.
7. In the second experiment the enzymes were studied in
mesenteric arterioles. A significant increase in blood
pressure occurred only in the deoxycortone-treated rats. A
significant increase in alkaline phosphatase and in glucose-6-
phosphate dehydrogenase activity in mesenteric arterioles
occurred only in this group. There was a trend for arteriolar
alkaline phosphatase activity to decrease with increasing
weight of the animals. This was not significant in normal-19V
animals but was so in uninephrectomised rats. The trend for
the increase in arteriolar glucose-6-phosphate dehydrogenase
activity to be greater in animals with the greater increase in
blood
pressure failed to reach conventional levels of signi¬
ficance.
No differences were observed in the mean values of the
activities of lactate dehydrogenase or malate dehydrogenase
in the arterioles of the four
groups of rats.
8. A comparison of the enzyme activities measured
suggested that whereas cardiac muscle has a greater capacity for
metabolism by glycolysis and the citric acid cycle the pentose
phosphate pathway is more important in arteriolar tissue.
9. Neither in cardiac tissue nor in arteriolar tissue of
hypertensive animals were there alterations in the enzymes of
the glycolytic pathway or the citric acid cycle, the main
energy-supplying routes of metabolism. The activities of the
enzymes altered are known to be under hormonal control. The
small amount of evidence there is on vascular tissue
enzymes suggests that the variation in the enzyme activities in the early
stage of experimental hypertension is possibly determined by a
pituitary or adrenal dysfunction initiated by the sodium load.
10. The enzyme changes which occurred in the different
groups of animals in arteriolar tissue showed a closer relationship to the capacity of the given treatment for increasing blood
pressure and producing arteriolar damage than those which occurred in cardiac tissue.
11. Further studies are
necessary to determine if the
observed changes in the vascular enzymes are also found at an-195-
early stage in other forms of experimental hypertension. A
study of the enzymes in arterioles from human biopsy material
from hypertensive patients would establish the relationship of these observations in experimental disease to the human condition
uninephrectomised rats, salt-loaded rats and normal animals were
maintained under identical conditions.
