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Biomedical subjects

A V Edwards

Publications and source records attributed to A V Edwards.

At least 91 records · Page 5Linked to original sources

Parotid responses to stimulation of the parasympathetic innervation in bursts in weaned lambs.

1. The effects of stimulation of the peripheral end of the parotid nerve in 1 sec bursts at 10 sec intervals has been investigated in weaned Suffolk lambs 3-4 months after birth.2. Stimulation in bursts at either 10 or 20 Hz for 10 min produced a significantly greater flow of parotid saliva, output of Na(+) and K(+) and fall in parotid vascular resistance (p.v.r) than continuous stimulation at the corresponding constant frequency (1 or 2 Hz) for the same period.3. Stimulation at 40 Hz in bursts for the same period produced a significantly greater output of K(+) and fall in p.v.r. than continuous stimulation at 4 Hz, whereas the salivary flow rates and Na(+) outputs were closely similar.4. Comparison of the effects of stimulation of the parotid nerve in bursts over a wide range of frequencies showed that each of these parotid responses was maximal at about 80 Hz.5. Parotid salivary responses to continuous stimulation of the parotid nerve at 20 Hz for 10 min were effectively abolished by prior administration of atropine (> 1.0 mg/kg), whereas the percentage fall in p.v.r. was merely reduced from 80.2+/-3.6 to 33.1+/-8.3% under the same conditions. There was no significant change in the mean arterior-venous difference in the plasma concentration of vasoactive intestinal peptide, substance P or somatostatin, in either the presence or absence of atropine in these experiments.6. The results are discussed in relation to the proposition that the enhancement of parotid responses which is observed during intermittent stimulation of the parasympathetic innervation at relatively high frequencies under experimental conditions also occurs normally in conscious sheep.

Animals↗

Recent physiological studies of the alimentary autonomic innervation.

The optimum pattern of stimulation of the VIP-ergic fibres in the submaxillary gland of the cat has been investigated by comparing the effects of continuous stimulation at 2 Hz for 10 min with those of stimulation at 20 Hz for 1 sec intervals for the same period. Both the fall in submaxillary vascular resistance (SVR) and release of VIP from the gland are significantly increased when the same total number of impulses is delivered in bursts at the higher frequency. Comparison of submaxillary responses to stimulation in 1 sec bursts, over a wide range of frequencies, has shown that, in atropinised cats, the fall in SVR is linearly related to stimulus frequency over the range 2-60 Hz, and maximal at 80 Hz. In addition, the fall in SVR is linearly related to stimulus frequency over the range 2-60 Hz, and maximal at 80 Hz. In addition, the fall in SVR is linearly related to log VIP output from the gland over the whole of the frequency range 2-160 Hz. Stimulation in 1 sec bursts at 10 sec intervals has also shown that certain non-peptidergic autonomic responses are optimal at much higher stimulus frequencies than has hitherto been supposed on the basis of classical studies employing continuous stimulation. It is concluded that it is no longer justified to assume that autonomic nerve fibres are invariably characterised by low natural discharge frequencies or that they necessarily fire at relatively constant rates. The results obtained using bursts of stimuli also show how differential responses can be obtained in the same tissue simply by varying the stimulus frequency and pattern.

Animals↗

Pancreatic endocrine responses to exogenous neurotensin in the conscious calf.

1. Responses to neurotensin have been investigated in conscious calves 2-5 weeks after birth given continuous I.V. infusions of the peptide for 15 min (5 pmol. kg-1 . min-1). 2. In control calves the concentration of the peptide in the arterial plasma had risen by 160 +/- 10 pmol/l at the end of the infusion,. after which it fell exponentially (t1/2: 1.4 min). 3. This dose of neurotensin produced no significant change in mean heart rate, aortic blood pressure, plasma gastrin or glucose concentration. 4. It was found that neurotensin could produce a pronounced rise in the concentration of both insulin and pancreatic polypeptide (PP) in the arterial plasma, together with a much smaller rise in pancreatic glucagon concentration. 5. Each of these three pancreatic endocrine responses was found to be glucose-sensitive within the range ca. 5.0-9.0 mmol/l. Hyperglycaemia potentiated insulin release and inhibited release of PP and glucagon. 6. The results are discussed in relation to the findings of other workers in other species.

Animals↗

Developmental changes in pancreatic endocrine function in the young calf.

1. Pancreatic endocrine responses to 2-deoxyglucose (1.2 mmol/kg I.V.) known to be mediated via the autonomic innervation, have been investigated in calves 24 h after birth and the results compared with those obtained previously in older calves (Bloom, Edwards & Hardy, 1978). 2. Neurally mediated insulin release was found to be defective in the calf at 24 h, whereas the capacity to release both pancreatic glucagon and pancreatic polypeptide (PP) in response to 2-deoxyglucose appears to be fully developed at this age. 3. Both the release of glucagon and of PP from the pancreas which occurred under these conditions were suppressed by I.V. infusions of glucose (17 mumol . kg-1 . min-1) which raised the arterial plasma glucose concentration of unsuckled 24-h-old calves to the level normally encountered in suckled calves of the same age. 4. Closely similar changes in the haematocrit and plasma cortisol concentration occurred in both suckled and unsuckled 24-h-old calves in response to 2-deoxyglucose, suggesting that the intensity of the stimulus to the brain was equipotent and that glucose inhibits the release of glucagon and PP by a direct action on the alpha and PP cells respectively. 5. closely similar changes in plasma PP concentration were observed in suckled and unsuckled 24-h-old calves in response to 2-deoxyglucose, in spite of the higher plasma glucose concentration in the former group. It is concluded that the PP response is potentiated by some unidentified factor in suckled calves.

Aging↗

The role of the parasympathetic system in the control of insulin release in the conscious calf.

1. The effect of atropine (0.2 mg/kg) on the release of insulin from the pancreas, in response to both exogenous and endogenous hyperglycaemia, has been investigated in conscious 2- to 5-week-old calves. 2 The rise in mean plasma insulin concentration in response to infusions of glucose, which raised the concentration of glucose in the plasma by about 4.0 mmol/l, was significantly depressed in calves with cut splanchnic nerves by prior administration of atropine. 3. The rise in plasma insulin concentration, which normally follows stimulation of the splanchnic nerves in the conscious calf (Bloom & Edwards, 1980), was almost completely suppressed by prior administration of atropine. 4. These findings are discussed in relation to those of other workers with other species. The results indicate that the parasympathetic innervation to the pancreas plays an important part in the control of insulin release in response to hyperglycaemia.

Animals↗

Pancreatic endocrine responses to stimulation of the peripheral ends of the vagus nerves in conscious calves.

1. The effects of stimulation of the peripheral ends of both vagus nerves below the heart (10 Hz for 10 min) were investigated in conscious calves 2-5 weeks after birth. 2. Stimulation was invariably below behavioural threshold and caused a prompt increase in the concentrations of pancreatic glucagon, insulin and pancreatic polypeptide (PP) in the arterial plasma. Each of these responses was blocked by pretreatment with atropine (0.2 mg/kg). 3. Administration of exogenous glucose by continuous I.V. infusion (ca. 0.08 mmol kg-1 min-1) greatly enhanced the release of insulin in response to vagal stimulation without significantly changing that of pancreatic glucagon or PP. 4. Vagal stimulation also caused a significant rise in the concentration of vasoactive intestinal peptide (VIP) in the intestinal lymph and this response was found to persist in the presence of atropine.

Animals↗

Pancreatic endocrine function in cortisol-treated thyroidectomized calves.

1. Pancreatic endocrine function has been investigated in thyroidectomized calves given exogenous cortisol (2.0 mg.kg-1.day-1) in order to produce overt signs of diabetes. 2. Whenever this diabetic syndrome was induced it was associated with falling plasma insulin concentrations. A few days later, there was a significant rise in the post-absorptive concentration of both pancreatic glucagon and pancreatic polypeptide (PP) in the arterial plasma. Elevated levels of both hormones invariably persisted until the animals were given thyroxine. 3. Each of the pancreatic endocrine responses to cortisol was reversed by daily administration of thyroxine (25 microgram.kg-1. day-1) and the plasma glucose concentration was restored to normal within a few days. 4. Starvation was found to be an extremely effective way of reducing both the plasma glucose and glucagon concentration of diabetic calves without apparently affecting the concentration of either insulin of PP. 5. Neurally mediated release of insulin in response to 2-deoxyglucose, but not of either pancreatic glucagon or PP, was found to be defective in diabetic calves and recovered in response to thyroxine. 6. These results suggest that the primary defect that leads to the development of this diabetic syndrome in cortisol-treated thyroidectomized calves is failure of insulin release but that this is associated with consequential changes in the rates at which both glucagon and PP are released from the pancreas.

Animals↗

Pancreatic endocrine responses to physiological changes in plasma neurotensin concentration in the calf.

1. Plasma neurotensin concentration was found to increase by between 3 and 18 pmol/l 20 min after feeding in conscious 2-6 week old calves. 2. Synthetic bovine neurotensin was infused I.V. at a dose which reproduced the rise in the plasma concentration (1 pmol. kg-1 min-1), in calves of the same age, which were also receiving a continuous I.V. infusion of glucose (0.03 mmol. kg-1. min-1) to mimic alimentary hyperglycaemia. Under these conditions neurotensin caused a significant rise in the mean concentration of both insulin and pancreatic polypeptide (PP), but not that of glucagon, in the arterial plasma. 3. The rise of plasma insulin concentration, but not that of PP, in response to the same dose of neurotensin was strongly potentiated during infusions of exogenous amino acids. There was also a significant rise in plasma glucagon concentration in response to neurotensin in the calves given amino acids. 4. It is concluded that neurotensin is a physiological incretin in the calf.

Animals↗

Effects of autonomic stimulation on the release of vasoactive intestinal peptide from the gastrointestinal tract in the calf.

1. The effects of autonomic stimulation on the release of vasoactive intestinal peptide (VIP) from the gastrointestinal tract have been investigated in adrenalectomized claves 2-5 weeks after birth.2. Stimulation of the peripheral ends of the splanchnic nerves (10 Hz for 10 min) caused a small fall in the concentration of VIP in portal and arterial plasma, together with a rise in the concentration in intestinal lymph. None of these changes achieved statistical significance.3. The effects of stimulation of the peripheral ends of the thoracic vagi, below the heart (10 Hz for 10 min), were found to depend in part upon the integrity of the splanchnic sympathetic innervation. A substantial rise in the concentration of VIP in intestinal lymph occurred whether or not the splanchnic nerves had been cut whereas an associated rise in arterial plasma VIP was only observed in calves in which the splanchnic nerves had been sectioned.4. The rise in the concentration of VIP in intestinal lymph, in response to vagal stimulation, was unaffected by concomitant stimulation of the splanchnic nerves, although the associated rise in arterial plasma VIP concentrations was suppressed. The response was also found to be resistant to atropine.5. The minimum estimated concentration of VIP in the extracellular fluid of the gastrointestinal tract was estimated to be about 60 p-mole/l. at rest and to rise by 70-120 p-mole/l. in response to vagal stimulation.6. Intravenous infusions of VIP at a dose of 50 ng kg(-1) min(-1) (16 p-mole kg(-1) min(-1)), which raised the minimum estimated concentration of VIP in the gastro-intestinal tract to the highest range encountered during stimulation, produced no significant changes in the concentrations of glucose, insulin, pancreatic glucagon or pancreatic polypeptide in the arterial plasma.7. It is concluded that a small amount of VIP is released from the gastrointestinal tract in response to vagal stimulation. In contrast, release of VIP is unaffected by stimulation of the splanchnic nerves except in so far as the rate at which the peptide passes into the circulation is reduced by adrenergic vasoconstriction.

Animals↗

Vasoactive intestinal peptide in relation to atropine resistant vasodilatation in the submaxillary gland of the cat.

1. Release of VIP from the submaxillary gland, in response to stimulation of the chorda tympani, and its vasodilator action at the site of release have been investigated in anaesthetised cats. 2. Chorda stimulation at 20 Hz produced an abrupt rise in the concentration of VIP in the submaxillary venous effluent plasma, accompanied by a substantial increase in submaxillary blood flow, in the presence or absence of atropine. 3. Intra-arterial infusions of VIP which reproduced the rise in submaxillary venous plasma concentration that occurred during chorda stimulation at 20 Hz, also produced a rise in submaxillary blood flow of the same order of magnitude. 4. Direct comparison of the responses of the submaxillary vasculature to intraarterial infusions of VIP, ACh and bradykinin showed that the vasodilator potency of VIP far exceeded that of either of the other agonists. 5. Intra-arterial infusion of ACh, sufficient to elicit a maximal submaxillary vasodilator response, caused no detectable release of VIP from the gland. 6. The results are discussed in relation to the proposition that VIP is released from post-ganglionic parasympathetic neurones, in the submaxillary gland of the cat, and acts, as a transmitter, to cause vasodilatation, which is resistant to atropine.

Acetylcholine↗

Adrenal medullary responses to stimulation of the splanchnic nerve in the conscious calf.

1. Right adrenal medullary and various cardiovascular responses to stimulation of the peripheral end of the right splanchnic nerve have been investigated in conscious calves, 2--5 weeks after birth. 2. The output of both adrenaline and noradrenaline was linearly related to stimulus frequency over the range 2.0--10.0 Hz, 2 1/2 min after stimulation was initiated. Peak outputs of both amines were obtained in response to stimulation at 15.0 Hz. 3. The output of adrenaline invariably exceeded that of noradrenaline, roughly in the proportion 3:2. At all frequencies tested between 7.0 and 40.0 Hz this difference was statistically significant (P less than 0.1). 4. Continuous stimulation at either 4.0 or 10.0 Hz produced a small but significant rise in the output of dopamine-beta-monooxygenase (DBH) activity from the right adrenal gland. Mean maximal outputs were obtained after 10 min; the levels were closely similar at both 4.0 and 10.0 Hz and could not be related to stimulus frequency or to the output of either adrenaline or noradrenaline. 5. The results are discussed in relation to perfusion studies in vitro and experiments in anaesthetized animals. It is concluded that the levels of DBH in adrenal effluent plasma is an unreliable index of catecholamine exocytosis in the conscious calf.

Adrenal Medulla↗

The effect of somatostatin on pancreatic endocrine responses mediated via the parasympathetic innervation in the conscious calf.

1. The effect of somatostatin on the responses to moderate insulin hypoglycaemia and to 2-deoxyglucose has been examined in 2--3 week-old calves with cut splanchnic nerves. 2. Intravenous infusions of somatostatin (150 p-mole . kg-1 . min-1) completely suppressed release of glucagon, pancreatic polypeptide (PP) and insulin from the pancreas in response to 2-deoxyglucose (1.1 m-mole/kg I.V.). 3. The same dose of somatostatin completely blocked the rise in plasma PP concentration that normally occurs in response to moderate insulin hypoglycaemia and significantly delayed the rise in plasma pancreatic glucagon concentration. The hypoglycaemic response to insulin was also found to be intensified by the administration of somatostatin. 4. It is concluded that each of the pancreatic neuroendocrine responses, that are now known to be mediated via the parasympathetic innervation, is suppressed in the presence of somatostatin in the young calf.

Animals↗

Pancreatic endocrine responses to stimulation of the peripheral ends of the splanchnic nerves in the conscious adrenalectomized calf.

1. Certain effects of stimulation of the peripheral ends of both splanchnic nerves have been investigated in unanaesthetized calves, given appropriate adrenal steroid replacement therapy. 2. Splanchnic nerve stimulation at frequencies within the physiological range produced prompt rises in the concentration of glucose, pancreatic glucagon and pancreatic polypeptide in the arterial plasma. These responses were followed by a rapid rise in plasma insulin concentration when the stimulus was terminated. The extent of this rise was related to the plasma glucose concentration at that precise point in time. 3. Stimulation at all frequencies tested had no effect on the concentration of vasoactive intestinal peptide in lymph collected from the intestinal duct. 4. The results are discussed in relation to those obtained in previous studies in anaesthetized calves of the same age.

Adrenalectomy↗

Responses to stimulation of the peripheral end of the right splanchnic nerve in the conscious calf.

The ratio at which adrenaline and noradrenaline are released from the adrenal medulla in response to stimulation of the splanchnic nerve has been established in the conscious calf. The proportion of adrenaline:noradrenaline was closely similar to that in which the 2 amines are stored in the gland and released in response to other stimuli in conscious, but not anesthetized, calves.

Adrenal Glands↗

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.

Animals↗