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Biomedical subjects

A V Edwards

Publications and source records attributed to A V Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1978

Certain pharmacological characteristics of the release of pancreatic glucagon in response to stimulation of the splanchnic nerves.

1. The effect of alpha- and beta-adrenoceptor blockade on the release of pancreatic glucagon, in response to stimulation of the peripheral ends of the splanchnic nerves has been examined in adrenalectomized calves 3-5 weeks after birth. In addition, the effects of insulin, atropine and somatostatin on the glucagon response to splanchnic nerve stimulation have been assessed in adrenalectomized dogs. 2. In calves release of pancreatic glucagon in response to splanchnic nerve stimulation was not suppressed by phentolamine at a dose that effectively abolished alpha-adrenergic inhibition of insulin release, or by propranolol, at a dose that completely eliminated the chronotropic action of the cardiac sympathetic innervation. 3. In dogs release of pancreatic glucagon in response to splanchnic nerve stimulation was not suppressed by atropine (0.2 mg/kg) or somatostatin, at a dose that caused a steady fall in the concentration of gastrin in the circulating plasma (0.5 microgram-kg-1 min-1). Glucagon release was apparently potentiated by exogenous insulin (4.0 u./kg). 4. The results are discussed in relation to the findings of other workers and it is concluded that the precise mechanism whereby stimulation of the sympathetic innervation to the pancreas leads to secretion of glucagon merits more detailed investigation.

Adrenalectomy↗
PubMed1978

The role of the autonomic nervous system in the control of pancreatic endocrine responses to milk ingestion in the calf.

1. Pancreatic endocrine responses to ingestion of milk have been investigated in conscious unweaned calves, 3-5 weeks after birth. Passage of gastric content from abomasum to small intestine was prevented by means of a cannula placed in the duodenum adjacent to the pylorus and food was witheld for at least 22 h in order to deplete liver glycogen. 2. Under these conditions ingestion of milk was followed by a prompt rise in the concentrations of pancreatic glucagon, PP and gastrin in the arterial plasma but the usual rises in plasma glucose and insulin concentration were absent. 3. Evidence was obtained to show that absorption of glucose from the small intestine occurs sufficiently rapidly to account for the initial rise in plasma glucose concentration after feeding in normal animals. However, the rise in plasma glucagon concentration was sufficient to contribute to alimentary hyperglycaemia by promoting hepatic glycogenolysis in calves with abundant liver glycogen. 4. None of the neuroendocrine responses to ingestion of milk was affected by prior section of the splanchnic nerves whereas each was blocked by atropine (0.2 mg/kg), showing that all depend upon muscarinic, parasympathetic rather than sympathetic activity, in the absence of extraneous stress.

Animals↗
PubMed1977

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.

Adrenal Glands↗
PubMed1976

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

1. Pancreatic and adrenal responses to intense hypoxia have been examined in conscious unrestrained calves 3-5 weeks after birth. 2. The outputs of both cortisol and corticosterone from the right adrenal gland rose steadily in response to hypoxia and this cortical secretory response was accompanied by a pronounced increase in blood flow through the gland. The changes in both steroid output and adrenal blood flow corresponded with those which occur in response to supramaximal doses of corticotrophin in calves of the same age. 3. Neither adrenaline nor noradrenaline were released in significant amounts from the adrenal medulla until the arterial PO2 had fallen below 15 mmHg. Such severe hypoxia caused secretion of catecholamines at rates comparable with those recorded during maximal stimulation of the sympathetic innervation to the gland in anaesthetized calves. The response to intense hypoxia in these conscious calves differed from that which occurs under anaesthesia in that the amount of adrenaline released was invariably greater than that of noradrenaline. 4. Severe hypoxia produced a rapid but transient increase in plasma glucagon concentration, followed by a pronounced rise in plasma glucose concentration in animals with abundant liver glycogen. No change in plasma insulin concentration was observed during hypoxia although it rose subsequently in response to hyperglycaemia. 5. Bilateral section of the splanchnic nerves virtually abolished the release of catecholamines in response to hypoxia but the adrenal cortical and pancreatic responses did not appear to be affected.

Adrenal Glands↗
PubMed1975

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.

Adrenal Glands↗
PubMed1975

The sensitivity of adrenal responses to synthetic adrenocorticotrophin in the conscious unrestrained calf.

1. Changes in cortisol and corticosterone output and blood flow from the adrenal gland have been determined in the conscious unrestrained calf during I.V. infusions of synthetic adrenocorticotrophin (Synacthen) at 0-5 ng-kg(-1) min- minus 1 (low dose), 5 ng-kg- minus 1 (medium dose), 50 ng-kg- minus 1 min- minus 1 (high dose) and 500 ng-kg- minus 1 min- minus 1 (medium dose), 50 ng-kg- minus 1 min- minus 1 (high dose) and 500 ng-kg- minus 1 min- minus 1(very high dose). 2. Infusions at the low dose produced a rise in adrenal output of both cortisol and corticosterone to maximum values of approximately 100 and 30 ng-kg- minus 1 min- minus 1 respectively. Mean output of both steroids was significantly increased within 5 min, reached a maximum within 10 min and had fallen to resting levels 10 min after the infusion was discontinued. 3. The effects of infusions at both the high and very high doses were closely similar; maximal cortisol outputs were within the range 600-800 ng-kg- minus 1 min- minus 1 and corticosterone 350-500 ng-kg- minus 1 min- minus 1 in both groups. 4. When the infusions were terminated, pronounced differences were observed in the rates at which steroid outputs declined. Basal levels were restored within 10 min following the low dose and within 60 min in medium dose animals, but both cortisol and corticosterone output were still elevated 2 hr after infusion in high dose animals. In calves infused at the very high dose, cortisol output did not fall significantly during 2 hr period. The ratio of cortisol: corticosterone released from the adrenal gland immediately before infusion (3-2 +/- 0-3) approximated to the proportions in which the two steroids were found in the arterial plasma, but fell progressively to a minimum (1-3 +/- 0-1) with increasing doses of Synacthen. Conversely, the ratio of the steroids in the arterial plasma was increased during infusions at the low dose, but not at the higher doses. 6. No significant change in adrenal blood flow occurred during Synacthen infusion in low dose animals despite the increase in steroid output. In medium dose animals blood flow through the gland rose during infusion by approximately 75 per cent while in both high and very high dose animals the flow increased by up to 300 percent. 7. In the three groups in which adrenal hyperaemia occurred, blood flow had fallen to within the resting range 45 min after infusion: in each case this fall was much more rapid than the fall in steroid output. No significant increase in aortic blood pressure or heart rate accompanied infusion of Synacthen, indicating that adrenal hyperaemia was dependent upon vasodilatation with the gland. 8. Administration of cycloheximide (10 mg/kg) by I.V. injection either before or during an infusion of Synacthen, inhibited steroidogenesis without affecting the vasodilator response.

Adrenal Glands↗
PubMed1975

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.

Age Factors↗
PubMed1975

The release of pancreatic glucagon and inhibition of insulin in response to stimulation of the sympathetic innervation.

The changes in the concentration of glucagon and insulin in arterial plasma which occur in response to splanchnic nerve stimulation have been investigated in adrenalectomized dogs, cats and sheep. 2. In dogs, stimulation of both splanchnic nerves at a low frequency (2-0 c/s) for 10 min produced a small but statistically significant increase in plasma glucagon concentration and appeared to inhibit the release of insulin. Stimulation at a higher frequency (10-0 c/s) produced a much greater increase in plasma glucagon concentration, which was normally accompanied by a rise in plasma glucose concentration. 3. Qualitatively similar changes in plasma glucagon and insulin concentration were observed in both sheep and cats in response to adrenergic stimulation. 4. Intramesenteric infusions of glucagon at a dose of 5-0 ng kg-1 min-1 in dogs produced a comparable rise in plasma glucagon concentration to that elicited by splanchnic nerve stimulation at high frequency (10-0 c/s) and invariably caused a rise in plasma glucose concentration. 5. In dogs given exogenous glucose, release of glucagon in response to splanchnic nerve stimulation was unaffected by induced hyperglycaemia. Secretion of insulin was partially inhibited by stimulation at 2-0 c/s and completely suppressed at higher frequency (10-0c/s). 6. It is concluded that stimulation of the sympathetic innervation to the pancreatic islets, at frequencies within thephysiological range, stimulates the release of glucagon and inhibits that of insulin in each of these species.

Adrenalectomy↗
PubMed1974

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.2. A pronounced rise in plasma glucagon concentration occurred in normal conscious calves in response to hypoglycaemia following administration of insulin (0.1 u./kg). Prior treatment with atropine caused no significant change in the hypoglycaemic response to insulin in these animals but the rise in plasma glucagon concentration was delayed.3. Section of both splanchnic nerves produced no significant change in the tolerance of conscious calves to this small dose of insulin and the changes in plasma glucagon concentration in these animals were within the normal range.4. In contrast, the same dose of insulin produced severe hypoglycaemia, accompanied by convulsions, in atropinized calves with cut splanchnic nerves. In spite of the intensity of the hypoglycaemic stimulus the rise in plasma glucagon concentration was both delayed and diminished in these animals.5. Administration of atropine alone (0.2 mg/kg) to normal fasting calves produced a significant fall in the mean plasma concentrations of both glucose and glucagon (P < 0.01) within 30 min, without affecting that of insulin.6. A significant increase in plasma glucagon concentration also occurred in response to stimulation of the peripheral ends of the thoracic vagi in adrenalectomized calves with cut splanchnic nerves under barbiturate anaesthesia. A rise in mean plasma glucose concentration was also observed in these experiments and found to be significantly correlated with the glucagon response.7. It is concluded that changes in either sympathetic or parasympathetic efferent activity may modify plasma glucagon concentration in the conscious calf, but that only the latter mechanism is likely to be implicated in the response to changes in plasma glucose concentration within the physiological range.

Animals↗
PubMed1974

The effects of infusions of synthetic adrenocorticotrophin in the conscious calf.

1. A technique is described by which the whole of the effluent blood from the right adrenal gland can be collected as required from conscious, unrestrained calves. The technique may be used to measure adrenal blood flow gravimetrically and to compute the output of adrenal hormones under various conditions in the normal calf.2. In a group of seven calves mean cortisol output from the right adrenal gland was found to vary between 20 and 40 ng.kg(-1) min(-1) and corticosterone between 6 and 18 ng.kg(-1) min(-1) during a 2 hr period, 24 hr after surgery.3. Intravenous infusions of synthetic adrenocorticotrophin (5 ng.kg(-1) min(-1)) produced a significant increase in the output of both cortisol and corticosterone within 5 min. The output of both hormones rose to maximal values within 10-20 min and mean values of approximately 300 ng.kg(-1) min(-1) (cortisol) and 120 ng.kg(-1) min(-1) (corticosterone) were maintained thereafter for the duration of the infusion (120 min). The output of both steroids fell to values comparable with those observed initially within 45-60 min after the infusion was discontinued.4. These changes in glucocorticoid output in response to adrenocorticotrophin produced a significant rise in the concentration of both cortisol and corticosterone in peripheral plasma. It is noteworthy that the rise in the mean corticosterone concentration in the peripheral plasma was substantially less than that which might be expected from relating the rise in mean plasma cortisol concentration to cortisol output.5. The results of control experiments have eliminated the possibility that the sampling procedure might itself increase steroid output or peripheral plasma concentration. Comparison of results from calves of widely disparate ages (8-38 days) provided no evidence that either the resting output of cortisol or corticosterone or the response to adrenocorticotrophin changes with age within the range examined.6. Infusion of adrenocorticotrophin (5 ng.kg(-1) min(-1)) also stimulated an abrupt rise in adrenal blood flow; mean resting flow (210 +/- 23 mul.kg(-1)) increased by approximately 30% within 5 min and attained peak values (355-365 mul.kg(-1) min(-1)) between 10 and 30 min. Thereafter, adrenal blood flow steadily decreased and then fell rapidly to within the resting range when the infusion was terminated. No significant changes in heart rate or aortic blood pressure occurred during these infusions.7. The results are discussed in relation to those obtained in other species and under differing conditions by other workers.

Adrenal Glands↗
PubMed1973

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.2. Stimulation of the peripheral ends of both splanchnic nerves (0.5-10.0 c/s for 10 min) caused an abrupt increase in plasma glucagon concentration in adrenalectomized calves 3-5 weeks after birth. This effect was found to be statistically significant (P < 0.01) at each of these frequencies. In calves tested during the first 24 hr after birth comparatively small responses were obtained.3. The hyperglycaemia produced by splanchnic nerve stimulation in older calves caused an abrupt rise in plasma insulin concentration when stimulation was discontinued but insulin release was completely inhibited throughout the period of stimulation at all frequencies tested.4. It is concluded that tonic changes in sympathetic efferent activity are likely to modify plasma glucagon concentration in the normal conscious calf.

Adrenal Glands↗