Studies on the mechanisms of ACTH-induced inhibition of aldosterone biosynthesis in the rat adrenal cortex.

In rats, chronic treatment with high doses of ACTH (10-40 micrograms/100 g body weight per day) leads to a marked reduction in aldosterone synthesis by adrenal capsules. The possibility that this inhibition is secondary to a decrease in plasma potassium levels or in renin angiotensin system (RAS) activity has been explored. The effects of chronic ACTH treatment were compared in (I) animals in which the endogenous RAS activity was stimulated by restricting dietary sodium intake, (II) animals in which plasma angiotensin II was increased by infusion from implanted osmotic minipumps and (III) animals which received supplementary potassium and in which hypokalaemia was prevented. In all cases, rates of aldosterone biosynthesis in vitro by adrenal capsules were decreased in ACTH-treated animals to an extent similar to those in untreated controls. In addition, ACTH treatment of hypophysectomized rats resulted in a similar inhibition of aldosterone biosynthesis to that found in sham-operated controls. It may be concluded that the ACTH-induced reduction of aldosterone biosynthesis is independent of the secretion of other pituitary hormones, and cannot be simply ascribed to either a reduction in RAS activity or in plasma potassium levels. The results are consistent with the view that the effects of chronic ACTH treatment are mediated by a direct action on the zona glomerulosa cell, which leads to its transformation into a zona fasciculata-like form.

Effect of electrolytic lesions of the medullary inspiratory region in rats.

The medulla oblongatas of 48 anesthetized rats were explored by electrical stimulation. The pneumotachogram and in some, the arterial blood pressure as well, were recorded. The inspiratory area was located in the ventral reticular formation from the obex to 1.8 mm rostral to the obex. It occupied about 2.2 mm3 on each side of the midline. The expiratory reactive points were scattered in a region which was dorsal and caudal to the inspiratory area. Unilateral and midline lesions produced by 3, 5 and 8 ma direct current did not stop rhythmic respiration. There was an initial increase in the respiratory rate followed by diminution to below that of the prelesion time. The respiratory air flow was decreased. The changes in respiratory rate and air flow were not statistically significant in majority of the above groups. Bilateral lesions produced by 3 or 5 ma stopped breathing. Continuation of thythmic respiration after destruction of a number of inspiratory neurons and/or fibers in the midline or one side of the medulla indicates that all the inspiratory neurons and fibers are not essential for the maintenance of respiration. Cessation of thythmic respiration after destruction of all or most of inspiratory neurons on both sides of the midline indicates the essential role of the medulla-oblongata for genesis or maintenance of rhythmic respiration.