A V Edwards

The role of the sympathetic innervation in the control of plasma glucagon concentration in the calf

1. The extent to which the splanchnic sympathetic innervation is implicated in the control of plasma glucagon concentration has been investigated in the young calf.

The role of the autonomic innervation in the control of glucagon release during hypoglycaemia in the calf

1. The extent to which the autonomic innervation to the pancreas is implicated in the control of glucagon release during hypoglycaemia has been investigated in calves 3–6 weeks after birth.

The role of the autonomic nervous system in the control of glucagon, insulin and pancreatic polypeptide release from the pancreas.

1. The mechanisms of release of pancreatic glucagon, insulin and pancreatic polypeptide (PP) in response to hypoxia and to 2‐deoxyglucose have been investigated in conscious calves 3‐5 weeks after birth. 2. A single injection of 2‐deoxyglucose (200 mg/kg I.V.) produced an abrupt rise in the concentrations of pancreatic glucagon, insulin and PP in the arterial plasma. The changes in plasma insulin and PP concentration were unaffected by prior section of the splanchnic nerves but were effectively abolished by atropine (0‐2 mg/kg I.V.). The rise in plasma pancreatic glucagon concentration was prevented in calves with cut splanchnic nerves that were given atropine but neither procedure alone suppressed the response. 3. 2‐deoxyglucose also caused a substantial increase in the output of glucocorticoids from the right adrenal gland together with a pronounced rise in adrenal blood flow. There was also a small but significant increase in catecholamine output from the adrenal medullae in these animals. 4. Intense hypoxia caused a pronounced increase in the concentration of PP in the arterial plasma. This was found to resemble the glucagon response to intense hypoxia in that it persisted in animals with cut splanchnic nerves that were given atropine. Less intense hypoxia caused a rise in plasma pancreatic glucagon concentration (but not PP) that was abolished by section of the splanchnic nerves. The changes in plasma insulin concentration in these experiments were consistent with the conclusion that they were secondary to changes in plasma glucose concentration. 5. It is concluded that pancreatic endocrine responses to both moderate hypoxia and 2‐deoxyglucose are mediated by the autonomic innervation.

Cardiovascular and endocrine responses to feeding in the young calf.

A number of cardiovascular and endocrine responses which occur during and after feeding in the unweaned calf are described. 2. There was a substantial increase in both heart rate and mean aortic blood pressure during feeding in these animals. This occurred within the first few seconds and persisted throughout the period of ingestion. 3. The concentrations of glucose, insulin and gastrin in arterial plasma rose abruptly during, or immediately after, feeding and elevated values persisted for at least 2 hr. A transient increase in glucagon concentration was also observed. In contrast, feeding appeared to produce no immediate rise in enteroglucagon concentration. 4. The adrenal output of glucocorticoids rose transiently in response to feeding but that of catecholamines was unaffected. 5. Cardiovascular responses to feeding were also examined in other species. In unweaned kids the changes were essentially similar to those observed in the calf but were less pronounced. In lambs a persistent hypertension occurred which was associated with a brief initial tachycardia. In adult dogs ingestion of solid food also caused tachycardia but although the aortic blood pressure rose for a short period at the beginning of feeding, hypotension developed thereafter. 6. The possibility that both the cardiovascular and endocrine responses, which occur during or immediately after feeding, are mediated by the autonomic nervous system is discussed.

The glycogenolytic response to stimulation of the splanchnic nerves in adrenalectomized calves.

1. The effects of stimulation of the peripheral ends of one or both splanchnic nerves have been investigated in adrenalectomized calves at different ages.

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.

Endocrine responses to exogenous bombesin and gastrin releasing peptide in conscious calves.

The effects of I.V. infusions of synthetic amphibian bombesin and porcine gastrin releasing peptide (GRP), at a dose of 5 pmol/kg. min for 30 min, have been investigated in conscious calves 3‐6 weeks after birth. The protocols produced a closely similar rise in the bombesin‐like immuno‐reactivity of the arterial plasma of 208 +/‐ 14 pmol/l (bombesin) and 210 +/‐ 32 pmol/l (GRP) which fell exponentially with a half‐life of about 3 min when the infusions were terminated. Neither peptide produced a discernible change in mean heart rate or aortic blood pressure, or in the mean arterial plasma concentrations of enteroglucagon, gastric inhibitory peptide (GIP), gastrin or cholecystokinin (CCK). GRP, but not bombesin, produced a small but significant rise in the mean plasma somatostatin concentration. Both peptides produced a significant rise in mean plasma pancreatic glucagon and pancreatic polypeptide concentration and proved to be exceptionally potent insulinotropic agents. These responses were associated with a rise in plasma glucose concentration which could not be attributed to a direct action of GRP on the liver. The distribution of bombesin‐like immunoreactivity in the gastrointestinal tract was consistent with the findings of other workers who have concluded that it is restricted to nerve terminals. However, our other findings show that GRP is capable of acting as a true hormone.

Adrenal and pancreatic endocrine responses to hypoxia and hypercapnia in the calf.

1. Adrenal and pancreatic endocrine responses to hypoxia and hypercapnia, of differing degrees of intensity, have been examined in conscious, unrestrained calves 3‐5 weeks after birth. 2. The outputs of cortisol and corticosterone from the right adrenal gland were found to vary inversely with arterial Po2 between 17 and 55 mmHg. Significant increase in mean adrenal blood flow was not observed at arterial oxygen tensions above about 30 mmHg. 3. Release of physiologically effective amounts of catecholamines from the adrenal medulla occurred only in response to intense hypoxia (arterial Po2 17‐1 +/‐ 2‐8 mmHg) and was effectively abolished by section of both splanchnic nerves. Release of pancreatic glucagon in response to such intense hypoxia was unaffected by section of both splanchnic nerves and administration of atropine. In contrast, the rise in plasma pancreatic glucagon concentration during less intense hypoxia was abolished by autonomic blockade. 4. Hypercapnia produced by inhalation of either 5% or 10% CO2 for 30 min stimulated maximal release of adrenal glucocorticoids and caused a substantial rise in plasma glucagon concentration. In contrast, the adrenal medulla was found to be extremely resistant to hypercapnia. Significant release of catecholamines was only observed during intense hypercapnia (inhalation of 10% CO2) and noradrenaline was invariably found to be the predominant amine. 5. The results of these experiments show how endocrine responses to hypoxia and hypercapnia are graded in the conscious calf. Of the mechanisms we have examined the pituitary‐adrenal cortical axis is the most sensitive and the adrenal medulla the most resistant, while the pancreatic alpha cell occupies an intermediate position.

Endocrine responses to insulin hypoglycaemia in the young calf.

1. Variations in the output of glucocorticoids and catecholamines from the right adrenal gland, in response to insulin hypoglycaemia, have been investigated in calves 2‐5 weeks after birth. These have been correlated with changes in the concentration of glucocorticoids and glucagon in arterial plasma. 2. Moderate hypoglycaemia for a limited period (0–1 u. insulin/kg), elicited a prompt increase in steroid output from the adrenal gland followed by a significant rise in plasma glucagon concentration. By comparison, changes in both catecholamine output and peripheral plasma glucocorticoid concentrations were found to be trivial in this group of animals. 3. Administration of a larger dose of insulin (0–5 u./kg) produced a more substantial fall in plasma glucose concentration followed by spontaneous recovery within 2‐3 hr. This stimulus elicited the release of greater amounts of both cortisol and corticosterone, followed by a significant increase both in the output of adrenaline and in plasma glucagon concentration. Increase in steroid output was accompanied by an increase in adrenal blood flow and was associated with elevated concentrations of both steroids in arterial plasma. 4. The adrenal cortical response and associated changes in plasma steroid concentration were found to be transient even in response to persistent and intense hypoglycaemia (4 u. insulin/kg). The increase in plasma glucagon concentration in this group of animals was not significantly greater than that produced by smaller doses of insulin. However, substantial amounts of adrenaline (78 plus or minus 14 ng. kg‐minus 1 min‐minus 1; maximum; n equals 9) together with a little noradrenaline (10 plus or minus 3 ng.kg‐minus 1 min‐minus 1; maximum; n equals 9) were released from the right adrenal gland under these conditions. 5. Changes in adrenal blood flow could be related to adrenal glucocorticoid output in calves given 0–1 or 0–5 u. insulin/kg. In animals given the largest dose of insulin adrenal blood flow was found to increase coincidentally with rising steroid output but this hyperaemia then persisted after steroid output had subsided to values within the normal range. 6. Calves given the largest dose of insulin (4–0 u./kg) invariably collapsed and convulsed after 2‐3 hr, but these symptoms could not be related to any particular endocrine response. No clinical signs of hypoglycaemia were observed in the other animals. 7. The results are discussed in relation to previous studies of adrenal function in this and other species.

Neuroendocrine responses to stimulation of the splanchnic nerves in bursts in the conscious adrenalectomized calf.

Effects of stimulation of the peripheral ends of the splanchnic nerves below behavioural threshold at either 4 or 2 Hz continuously for 10 min, and at 40 or 20 Hz for 1 s at 10 s intervals for 10 min, have been compared in conscious calves. Cardiovascular responses were apparently unaffected by the pattern of the stimulus, whereas pancreatic neuroendocrine responses were significantly enhanced by stimulation in bursts, as was the rise in mean arterial plasma glucose concentration. Release of bombesin‐like immunoreactivity was substantially potentiated by intermittent stimulation at relatively high frequencies and the significance of this discovery is discussed in relation to the effects that this peptide is known to evoke in this species.