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Desoxycorticosterone acetate (DOCA) was injected intramuscularly to pregnant rats at the III, or II-III trimester of pregnancy. By the end of pregnancy with increasing body mass of the female rats, the hormonal dosage dropped. The newborn rat skin was studied. The prenatal effect of DOCA resulted in thinning the epidermis, the decreasing dosage in certain activation of the epithelial proliferative activity and in appearance of foci of its hyperplasia. The hormone in the dose 0.8-1.0 mcg/100 g of the body mass activates the proliferative ability of fibroblasts, elevates the quantity of tissue basophils, increases secretory activity of both of them; this produces thickening of the derm. In the microvessels morphofunctional activity of endothelium increases, in the basal membrane contents of PAS-positive substances drop, the wall is often infiltrated with lymphocytes. Correlations between the cells and other structural components of the skin intensify. When the dose of DOCA increases and the time of the injection is short, the proliferative and secretory activity of fibroblasts is inhibited, but morphofunctional properties of the tissue basophils are stimulated. Congestive phenomena develop in the microvessels, mitotic activity of endotheliocytes is inhibited, in the basal membrane amount of the PAS-positive substances sharply decreases, perivascular edema develops in the connective tissue. Weakening or imbalance of the correlations is observed.
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We investigated the urinary excretion of phosphates, hydroxyproline, and cAMP in rats treated with desoxycorticosterone acetate (DOCA) associated with a hypersaline diet. We measured the three substances in groups with or without parathyroid or thyroid glands, or both. Urinary phosphate excretion increased greatly during the first weeks of treatment in normal rats and in rats autografted with parathyroids and lacking thyroid, and increased slightly in the groups without parathyroids. Hydroxyproline and cAMP had the same pattern; their excretion was greatest during week 2 of treatment in all groups, but these phenomena were more intense in animals with parathyroids. These fact support the conclusion that the parathyroid glands are stimulated during the start of mineralocorticoid-saline treatment.
To determine desoxycorticosterone acetate in oil injections, reverse phase partition chromatography on silanized, purified siliceous earth was used to separate the corticosteroid ester from the bulk of the oil vehicle. The latter was retained on the column while the steroid and the sterol and triterpenoid fractions of the oil were eluted. An internal standard was added to this eluate, which was then subjected to reverse phase high performance liquid chromatography (HPLC). The desoxycorticosterone acetate was quantitatively separated in the HPLC procedure from any free desoxycorticosterone, preservatives, and minor components of the oil. The suitability of the HPLC procedure was verified with a number of C18 packing materials, both pellicular and microparticular. The desoxycorticosterone acetate was adequately resolved from the internal standard, progesterone, with most C18 packing materials evaluated. The proposed procedure provides a suitable stability-indicating assay for desoxycorticosterone acetate in oil injections.
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The effect of desoxycorticosterone acetate (DCA) on the granulation tissue of healing and healed linear laparotomy wounds was studied in young adult male guinea pigs maintained on a complete diet and on a known intake of ascorbic acid. DCA induces the production of an excessive amount of granulation tissue, as evidenced by a relatively great number of fibroblasts and by a larger amount of ground substance. This effect was accompanied by a slight to moderate lag in the maturation process of both cellular and intercellular elements. These changes were observed when DCA administration was begun 5 days prior to operation, but were less obvious or absent if DCA was injected, beginning on the 5th or 10th postoperative day. The results indicate that the action of DCA on immature, proliferating connective tissue is marked, and is considerably less or absent when connective tissue elements have reached partial or almost complete maturity. The effect of DCA on connective tissue does not appear to rest on the basis of an altered nutritional status. Chemical and histochemical studies of the adrenals suggest that the action of DCA on connective tissue is probably mediated through a disturbance of adrenocortical function, namely an imbalance between hormones of the zona glomerulosa (excess of DCA) and those of the zona fasciculata (deficiency of glucocorticoids). The presence of changes in granulation tissue and the lack of them in mature resting connective tissue of DCA-treated guinea pigs confirm the view that a profound difference in the response mechanism exists between resting and actively proliferating connective tissue.
The experiment has been carried out on 6 bulls of cb. breed at the age of 3 months. Clearance methods were used to examine the hypophysin (0.1 u V/kg) and desoxycorticosterone acetate (0.1 mg/kg) influence on the size of diuresis, glomerular filtration and excretion of the following: sodium, potassium, chlorides, calcium, magnesium and inorganic phosphorus with urine. Three months old calves had (in comparing to calves in neonatal period) higher glomerular filtration level and lower coefficient of endogenous creatinine purification, however the GFR did not still reach the GFR level of adult animals. Hypophysin and desoxycorticosterone acetate influenced both the process of glomerular filtration (decrease) and tubular transportation of water, Na, K and Cl. After the acetate had been applied, higher condensation of urine was noticed than after the application of hypophysin. Administering DOC to the calves caused decrease in sodium and chlorides excretion with urine as well as increase in kidney purification of potassium. Increased excretion of potassium ion and the decrease in urine pH after DOC injection may suggest that older calves compared with the ones at the age of 2-5 weeks have their kidney mechanism regulating potassium and acid-basic balance developed and efficient. Significant effect of hypophysin and desoxycorticosterone acetate on the process of calcium, magnesium and inorganic phosphorus excretion with the urine has not been stated.
In the course of the development of desoxycorticosterone-acetate-salt hypertension the animals were noted to display high appetite of sodium chloride, a considerable increase of the weight of the heart, kidneys and adrenal glands, of the diameter of the glomeruli and the surface of the cortical and medullar zones of the kidneys, a decrease of the sodium and potassium gradient in the renal tissue. Adaptation to hypoxy is noted so cause a decrease in the interventricular factor, in the width of the glomerular zone of the adrenal glands, in the sodium concentration in the erythrocytes, an increase in the mass of the medullar layer of the kidneys, and an increase in the sodium and potassium gradients. When adaptation to hypoxy is combined with the effect of desoxycorticosterone-acetate-salt, hypertension develops to a lower degree than in non-adapted animals.
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