We studied the effects of hydrocortisone as a possible regulatory factor of bone blood flow and metabolism. Local bone blood flow in the tibia, distal femur, lumbar vertebra and some soft tissues (using 85Sr-microspheres), as well as 45Ca and 3H-proline incorporation into the tibia, bone density and ash weight per ml of the tibia were measured in sham-operated and oophorectomized female rats in which the influence of hydrocortisone administration (0.004 % diet for 5 weeks) was followed. Hydrocortisone markedly lowered 85Sr-microsphere uptake and blood flow through the bones of non-castrated female rats as well as elevated circulatory values in oophorectomized rats. The changes were nearly identical in the three bone samples measured; among the soft tissues only the kidneys showed a less pronounced decrease. Circulatory changes in the bones seem to be caused by local vascular reactions. Hydrocortisone also lowered the 24-hour incorporation of 45Ca and 3H-proline into the tibia of both non-castrated and oophorectomized females. In the tibia of oophorectomized rats, hydrocortisone normalized the decreased bone density and ash weight. The adrenocortical hormones are known to block eicosanoid synthesis by the inhibition of arachidonic acid production. It is possible, therefore, that local circulatory changes in the bones of rats, induced by hydrocortisone, are mediated by the changes in prostaglandin production.
Glucose tolerance, insulin secretion and in vitro insulin action were examined in streptozotocin-induced diabetic rats following pancreatic islet allotransplantation treated with combination of oral cyclosporine A (10 mg/kg) and hydrocortisone (1.5 mg/kg) intramuscularly. 1400 pure islets from multiple donors were implanted either into the portal vein (n = 10) or under the renal capsule (n=ll). Ten sham-operated non-diabetic animals receiving the same immunosuppressive therapy, 8 healthy animals without any treatment and 10 diabetic animals without immunosuppression following islet transplantation were used as controls. In all transplanted animals blood glucose was normalized by day 3 after transplantation with lower levels in those transplanted intraportally (p<0.05). Non-immunosuppressed animals rejected the graft after 6.5±1.2 days after transplantation, lmmunosuppressed animals in both groups remained normoglycaemic till the end of the experiment on day 28. Oral glucose tolerance tests and insulin levels on days 10 and 28 improved dramatically. No differences in glucose and insulin levels between intraportal and subcapsular groups were found. Post-load glucose levels in immunosuppressed non-transplanted animals were higher on day 28 than before treatment and were also higher than in the healthy non-treated group (p<0.05). In vitro insulin action determined by the incorporation of labelled glucose into adipose tissue was impaired only in animals in which islets were transplanted into the liver (p<0.05 vs other groups). In conclusion, therapy with cyclosporine A and hydrocortisone prevents allogeneic islet rejection in rats during a short-term experiment. Although glucose tolerance is not completely normalized following transplantation, slight impairment is also demonstrable in healthy animals on the same drug therapy.
The effect of chronic hydrocortisone administration (0.5 mg/kg) on the liver and plasma lipid content was assessed in Wistar rats. It was found after that the liver cholesterol content was significantly increased 6 months of hydrocortisone treatment. At the same time, the distribution of liver phospholipid fractions was altered. The fatty acid composition of liver lipids showed a significant increase of 22:6 n-3. Decreased levels of cholesterol and LDL-cholesterol were found in the plasma of the hydrocortisone-treated rats.