The development of the adrenal medulla of the foetal and new-born calf.

1. The output of adrenaline and noradrenaline from the adrenal medulla during asphyxia, stimulation of the splanchnic nerves or the intra-arterial injection of acetylcholine, has been investigated in foetal and new-born calves up to 3 weeks of age.2. Between 180 days' gestation and term ( approximately 281 days) the response of the foetal adrenal gland of the calf to asphyxia appeared to be independent of its nerve supply and the discharge consisted largely of noradrenaline. A similar type of discharge was obtained after the intra-arterial injection of acetylcholine, but stimulation of the splanchnic nerves resulted in only a small discharge of both adrenaline and noradrenaline.3. Rapid changes occurred in the response of the adrenal medulla to all forms of stimulation during the first 24 hr after birth. For the first 4-6 hr the adrenal medulla was hypersensitive; thereafter the response rapidly declined and a variable period of depressed excitability followed. The changes affected the output of noradrenaline rather than that of adrenaline and were more pronounced during asphyxia or after the intraarterial injection of acetylcholine. Within 24 hr of birth the amount of noradrenaline released in response to either form of stimulation was less than 25% of that found immediately after birth.4. During the hypersensitive phase immediately after birth splanchnic nerve activity appeared to potentiate the direct effect of asphyxia on the noradrenaline cells since the maximum output of noradrenaline was attained more rapidly and at a higher P(O2) if the splanchnic nerves were intact.5. The non-nervous direct response of the adrenal medulla to asphyxia decreased rapidly after birth and disappeared within 24 hr. It did not reappear at any age and was a feature of foetal life.6. The recovery of the response to acetylcholine occurred between 3 and 8 days after birth with a return of the high level of noradrenaline secretion; no similar increase in the output of adrenaline occurred at this stage.7. The response to asphyxia was not restored to the level found in the new-born calf until 2-3 weeks after birth. At this time the effect on the adrenal medulla appeared to be mediated almost entirely by the splanchnic nerves.8. The effects of chloralose and pentobarbitone anaesthesia on the changes in the nervous response to asphyxia after birth were compared. Essentially the same pattern of changes was found with both anaesthetics although the absolute level of discharge under chloralose was greater and a considerably larger amount of adrenaline was secreted at 3 weeks of age.9. At certain ages stimulation of the splanchnic nerves enhanced the response of the adrenal medulla to subsequent injections of acetylcholine. The noradrenaline output was only significantly increased by this procedure during the period of depressed excitability whereas the adrenaline discharge was always increased throughout the first 3 weeks of life.10. The changes in adrenaline and noradrenaline content of the adrenal glands during the 3-week period after birth were investigated. The noradrenaline concentration was low immediately after birth during the hypersensitive phase and increased during the period of reduced sensitivity. The output of this amine was thus inversely related to its content in the adrenal gland. A similar relation did not occur with adrenaline, the concentration of which remained relatively constant during the first 3 weeks of life.