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Study of vascular enzymes in experimental hypertension

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Date
1964
Author
Laing, Christine P.
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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.
 
URI
http://hdl.handle.net/1842/34935
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