EFFECTS OF INHIBITION OF ADRENAL STEROIDOGENESIS ON COMPENSATION OF FLUID LOSS AND ON SURVIVAL AFTER LIMB ISCHAEMIA IN THE RAT

Abstract

In rats injected with a specific inhibitor of adrenal steroidogenesis, 4α,5-epoxy-17β-hydroxy-3-oxo-5α-androstane-2α-carbonitrile (WIN 24 540), the increase in the concentration of corticosterone in the plasma caused by bilateral hind-limb ischaemia was greatly reduced. The lethality of this injury was increased. Fluid loss into the hind limbs was unaltered but the compensatory movement of fluid into the plasma was impaired. The hyperglycaemia that occurred after the injury was markedly reduced by WIN 24 540, but this was probably unrelated to the poorer compensation of fluid loss as there was no corresponding fall in plasma osmolality. The effects of injecting WIN 24 540 could be completely reversed by the simultaneous injection of corticosterone, so as to restore the rise in its concentration in the plasma. We conclude that the adrenal cortex plays an active part in the early circulatory and metabolic responses to injury, in contrast to its reportedly permissive role in the later catabolic phase.