The role of
ACTH
and of renin as mediators of the stimulating effect of haemorrhage on aldosterone secretion was investigated. The following experiments showed that release of
ACTH
is not indispensible for the effect: in non-hypophysectomized dogs with intact kidneys, in which the blood
ACTH
concentration was artificially raised by infusing
ACTH
, there was still a rise in aldosterone production after blood loss. Hypophysectomy did not abolish or reduce the response, in fact, it increased its frequency of occurrence in dogs in which steroid synthesis was maintained at a submaximal level by a constant infusion of
ACTH
. Another group of studies demonstrated that the release of renin is also not a necessary condition for the rise in aldosterone production after bleeding; dogs in which both kidneys had been removed, but the pituitary left intact, responded to bleeding by a rise in aldosterone secretion of the same magnitude as normal dogs. However, in the simultaneous absence of kidneys and pituitary gland aldosterone production did not rise after bleeding although the basic conditions for synthesis of steroids were provided by a constant infusion of
ACTH
. On the contrary, severe falls in steroid secretion rates were the rule. These falls were attributed to the fact that hypophysectomized-nephrectomized dogs often reacted to blood loss with collapse of the circulation, and it was possible to argue that this collapse, and not the absence of kidney and pituitary, might have prevented the rise in aldosterone secretion. Attempts were therefore made to improve the circulation by supplying pressor substances known to be released in haemorrhage: of these noradrenaline did not improve the tolerance to haemorrhage, angiotensin improved it only very slightly, but prolonged infusions of extracts of posterior lobe restored it nearly to normal. In some of these experiments, the post-haemorrhage fall in aldosterone secretion was also prevented, but a rise was never seen. Aldosterone secretion of the hypophysectomized-nephrectomized dog was stimulated by infusion of large volumes of donor blood obtained from dogs with intact kidneys which presumably contains renin, but not of blood from nephrectomized donors. No evidence was obtained for the existence of agents other than
ACTH
and angiotensin as mediators of the stimulating effect of haemorrhage on aldosterone secretion. Furthermore, these two agents could fully replace each other, as shown by the finding that the effect of haemorrhage was not diminished by either nephrectomy or hypophysectomy alone.
Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming
