Comparison of the hyperglycaemic and glycogenolytic responses to catecholamines with those to stimulation of the hepatic sympathetic innervation in the dog.

1. The effects of stimulation of the splanchnic innervation to the adrenal medullae, in dogs with cut hepatic nerves, were compared with those obtained previously in response to splanchnic and hepatic nerve stimulation in adrenalectomized dogs.2. Maximal stimulation of both adrenal medullae via the splanchnic innervation (20 c/s for 9 min), in dogs with cut hepatic nerves, produced closely similar hyperglycaemic and glycogenolytic responses to those obtained previously in adrenalectomized dogs with intact hepatic nerves.3. The rise in plasma glucose concentration in response to maximal stimulation of the adrenal medullae in dogs with intact hepatic nerves was found to be comparable to that which occurs in response to maximal stimulation of the hepatic sympathetic innervation alone. In contrast, the rise in haematocrit during maximal stimulation of the entire splanchnic innervation was substantially greater than that observed after removal of both adrenal glands.4. The output of adrenaline and noradrenaline from the left adrenal gland was determined during maximal stimulation of the left splanchnic nerve (20 c/s for 9 min). These results were then used to compute doses of the two amines which would reproduce the output of catecholamines from both glands under such conditions. The extent of the rise in mean plasma glucose concentration in response to these infusions was similar to that produced by maximal stimulation of both adrenal glands, but the duration of hyperglycaemia and depletion of liver glycogen were significantly less.5. Stimulation of the splanchnic innervation was found to produce an initial ;surge' in the release of catecholamines from the adrenal medullae, followed by a rapid decline in output when stimulation was continued for longer than 30 sec. Evidence was obtained which showed that this pattern of release is well suited to produce rapid mobilization of liver glycogen.6. Comparable changes in plasma glucose concentration occurred in response to stimulation of either the adrenal medullae or the sympathetic innervation to the liver at low frequency (2.0 c/s for 5 min). Stimulation of both pathways simultaneously, at the same frequency, produced smaller responses.7. Intramesenteric infusions of noradrenaline at 1.0 mug.kg(-1) min(-1) for 5 min produced comparable changes in plasma glucose concentration to those observed during stimulation of either pathway alone at low frequency. The mean plasma noradrenaline concentration of portal blood was raised by between 92 and 105 ng/ml. during these infusions.8. It is concluded that stimulation of either the splanchnic innervation to the liver, or of both adrenal medullae, at high frequency (20 c/s for 9 min) represents a supramaximal stimulus for hepatic glycogenolysis. Comparison of the responses to stimulation at low frequency (2.0 c/s for 5 min) suggests that the hepatic glycogenolytic mechanism is equally sensitive to stimulation via either route in this species.