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Biomedical subjects

A V Edwards

Publications and source records attributed to A V Edwards.

At least 73 records · Page 4Linked to original sources

Reduced adrenal cortical sensitivity to ACTH in lambs with cut splanchnic nerves.

The possibility that the sensitivity of the adrenal cortex to endogenous ACTH may be affected by splanchnic nerve activity has been investigated in conscious, weaned, 5- to 8-month-old lambs. The animals were atropinized (0.5 mg/kg) and tested with an i.v. infusion of noradrenaline (333 ng/kg per min for 10 min), which produced a significant rise in the mean concentration of both ACTH and cortisol in the arterial plasma. In lambs tested at least 7 days after section of both splanchnic nerves, just below the diaphragm, the rise in plasma ACTH concentration was significantly greater, and that in plasma cortisol significantly less, than in control lambs. The mean plasma ACTH and cortisol concentrations were linearly related to one another in both groups (r = 0.93 and 0.92) but the sensitivity of the adrenal cortex to the steroidogenic action of ACTH appeared to have been roughly halved 1 week after bilateral splanchnic nerve section.

Adrenal Cortex↗

Effects of certain metabolites on pancreatic endocrine responses to stimulation of the vagus nerves in conscious calves.

The effects of exogenous glucose (0.05 mmol/kg . min) and vamin (0.02 mmol/kg . min) on the pancreatic endocrine responses to stimulation of the peripheral ends of the vagus nerves have been investigated in conscious 3-6-week-old calves with cut splanchnic nerves. Exogenous glucose potentiated both the basal release of insulin and that which occurred in response to vagal stimulation, while inhibiting both the basal release of glucagon and that during vagal stimulation. Vamin significantly inhibited basal release of insulin but not that which occurred during vagal stimulation although it significantly inhibited vagal release of glucagon. The inhibitory effect of exogenous glucose on the basal and vagally stimulated release of pancreatic glucagon were both significantly reduced in the presence of vamin. Neither glucose nor mixed amino acids were found to affect the release of pancreatic polypeptide either at rest or during nerve stimulation. It is concluded that the effects of vagal activity on the alpha- and beta-cells of the islets of Langerhans are normally modified by the existing concentration of both glucose and amino acids in these animals.

Amino Acids↗

The role of the sympathetic system in the control of insulin release in response to hyperglycaemia in conscious calves.

The effects of the adrenoceptor blocking agents, phentolamine and propranolol, on the release of pancreatic glucagon and insulin in response to exogenous glucose have been investigated in conscious 2--6-week-old calves. There were no significant differences between the changes in mean plasma glucagon or insulin concentration, which occurred in response to hyperglycaemia, in calves pre-treated with both propranolol and phentolamine, phentolamine alone and normal calves. However, the rise in mean plasma insulin concentration was effectively abolished by pre-treatment with propranolol alone and there was a small but significant fall in mean plasma glucagon concentration which was not observed in any of the other groups. The results are discussed in relation to previous studies of the role of the autonomic innervation to the endocrine pancreas in the control of insulin release during hyperglycaemia in conscious calves and weaned lambs.

Animals↗

Pancreatic neuroendocrine responses to butyrate in conscious sheep.

The role of the autonomic innervation in the control of pancreatic endocrine responses to I.V. infusions of butyrate (0.02 mmol kg-1 min-1 for 10 min) has been investigated in conscious 4-6 month old weaned lambs. Intravenous butyrate produced a small rise in mean arterial plasma pancreatic glucagon concentration which was unlikely to have had any physiological effect and produced no consistent or statistically significant changes in mean plasma pancreatic polypeptide concentration in any of the groups studied. In contrast, butyrate produced an abrupt and substantial rise in mean plasma insulin concentration, which rose to a peak incremental value of about 300 pmol l-1 in normal control lambs. This response was unaffected by pre-treatment with either phentolamine or propranolol alone, but was significantly reduced by simultaneous administration of these drugs, as it was either by pre-treatment with atropine or prior section of the splanchnic nerves. The rise in mean plasma insulin concentration was inhibited most effectively by combined treatment with propranolol, phentolamine and atropine, which was significantly more effective than administration of atropine to lambs with cut splanchnic nerves (P less than 0.01). It is concluded that both divisions of the autonomic nervous system are likely to be involved in mediating the release of insulin from the pancreas, in response to butyrate, in this species under these experimental conditions and also in the resting state.

Animals↗

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.

Adrenalectomy↗

Characteristics of the neuroendocrine responses to stimulation of the splanchnic nerves in bursts in the conscious calf.

Neuroendocrine responses to splanchnic nerve stimulation in bursts (at 40 Hz for 1 s at 10 s intervals for 10 min) have been investigated in conscious adrenalectomized calves, 3-6 weeks after birth, in the presence of various pharmacological blocking agents. Preganglionic blockade with hexamethonium abolished all the neuroendocrine responses that were monitored. Pre-treatment with phentolamine significantly reduced, but failed to eliminate, the release of both pancreatic glucagon and pancreatic polypeptide. In the presence of phentolamine splanchnic nerve stimulation produced a massive rise in arterial plasma insulin concentration. None of these pancreatic neuroendocrine responses was significantly affected by additional pre-treatment with propranolol. The rise in mean plasma insulin concentration which occurred in calves pre-treated with both phentolamine and propranolol was significantly reduced by atropine. Release of bombesin-like immunoreactivity (BLI) was unaffected by total post-ganglionic adrenergic and cholinergic blockade. The results indicate that pancreatic endocrine responses to splanchnic nerve stimulation may be attributable, at least in part, to release of BLI in this species.

Adrenalectomy↗

Effects of certain metabolites on pancreatic endocrine responses to gastrin-releasing peptide in conscious calves.

The effects of intravenous infusions of synthetic gastrin-releasing peptide (GRP; 5 pmol/kg X min) have been investigated in 3- to 6-week-old conscious calves receiving continuous intravenous infusions of either glucose or amino acids or both at a dose of 0.03 mmol/kg X min and the results compared with the effects of the same dose of the peptide in control calves. Pre-treatment with amino acids alone caused a statistically significant fall in mean plasma glucose concentration, which was associated with a significant rise in mean pancreatic glucagon concentration. Additional infusion of glucose prevented this rise in plasma glucose concentration and resulted in a delayed, but very substantial rise in mean plasma insulin concentration. Pre-treatment with amino acids alone substantially and significantly increased the rise in mean plasma insulin that occurred in response to GRP. The rise in mean plasma glucagon concentration in response to GRP that occurred in the control group, the group pre-treated with amino acids alone and the group given both glucose and amino acids, was virtually eliminated in the group pre-treated with glucose alone. The normal rise in plasma pancreatic polypeptide concentration in response to GRP was invariably abolished in the presence of amino acids. No significant change in either mean neurotensin-like or gastric-inhibitory-peptide-like immunoreactivity was observed in response to GRP in any of these groups. The results are discussed in relation to possible physiological functions that GRP may subserve.

Amino Acids↗

Release of neuropeptide Y in response to splanchnic nerve stimulation in the conscious calf.

Plasma concentrations of neuropeptide Y were determined by means of a specific radioimmunoassay in the conscious calf. Significantly higher concentrations were found in the adrenal venous effluent (102 +/- 34 pmol/l) compared to systemic arterial plasma (11 +/- 7 pmol/l). Stimulation of the splanchnic nerves at 40 Hz in bursts for 1 s at 10 s intervals resulted in a slow sustained rise in plasma neuropeptide Y in both adrenal (peak 1124 +/- 217 pmol/l and peripheral (peak 771 +/- 182 pmol/l) samples. Experiments performed in adrenalectomized calves produced a closely similar release of neuropeptide Y when the nerves were stimulated intermittently in the same pattern and under the same conditions. Stimulation of the splanchnic nerves at 4 Hz continuously resulted in a smaller response. Pre-treatment with hexamethonium completely abolished the rise in plasma neuropeptide Y concentrations.

Adrenal Glands↗

Adrenal medullary responses to splanchnic nerve stimulation in new-born calves.

Right adrenal medullary and various cardiovascular responses to stimulation of the peripheral end of the right splanchnic nerve have been investigated in conscious calves 24-48 h after birth and compared with those obtained previously in older conscious calves. The results show that splanchnic nerve stimulation produces a smaller rise in mean aortic blood pressure and haematocrit in new-born calves than occurs in older animals. The fall in adrenal vascular resistance is also reduced, as is the amount of catecholamine released from the adrenal medulla, at 24-48 h. Although the absolute amounts of adrenaline and noradrenaline released in response to splanchnic nerve stimulation were significantly less in 24-48 h old calves, the ratio (3:2) was the same as that found in 2-5 week old animals and that in which the two amines are stored in the gland. The results confirm the contention that the sympathetic innervation is relatively immature immediately after birth in this species and that functional maturation occurs gradually over a period of weeks. However, they also show that the ratio in which adrenaline and noradrenaline are released from the adrenal medullae provide no index of this process, as had previously been suggested.

Adrenal Medulla↗

Neuropeptide Y (NPY) reduces myocardial perfusion and inhibits the force of contraction of the isolated perfused rabbit heart.

Isolated rabbit hearts, perfused under constant pressure (Langendorff technique) were used to study the effect of neuropeptide Y (NPY) on heart rate, force of heart contraction and rate of myocardial perfusion. No significant net change in heart rate was noted. A dose-dependent negative inotropic effect was consistently demonstrated which was characterised by slow onset and was often preceded by a transient positive inotropic response. Addition of small doses of NPY resulted in a prompt reduction in flow of the perfusate through the coronary vasculature. Since NPY is present locally in cardiac nerves, these effects may have physiological importance.

Acetylcholine↗

Neuroendocrine responses to stimulation of the vagus nerves in bursts in conscious calves.

Effects of stimulation of the peripheral ends of the vagus nerves below the heart at 4 Hz continuously, and at 40 Hz for 1 s at 10 s intervals, have been compared in conscious calves below behavioural threshold. Neither pattern of stimulation caused any significant change in mean aortic blood pressure or heart rate but both invariably produced a substantial increase in the flow of intestinal lymph. Each form of stimulation provoked release of glucagon, insulin and pancreatic polypeptide from the pancreas and produced a small but significant rise in mean arterial plasma glucose concentration. The release of gastric inhibitory peptide- and bombesin-like molecules from the gastrointestinal tract was not affected by vagal stimulation whereas release of vasoactive intestinal peptide was observed in response to both patterns of vagal stimulation. Evidence was obtained to suggest that gastrin-like peptides are preferentially released into the bloodstream whereas cholecystokinin-like peptides are not. Vagal stimulation releases somatostatin from the gastrointestinal tract but discontinuous stimulation seems to inhibit the release of somatostatin into the general circulation. The results that have been obtained, employing this particular protocol, suggest that the pattern of the stimulus that is applied to the vagal splanchnic innervation has relatively little effect on neuroendocrine response in this species.

Animals↗

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.

Animals↗

Neural vasodilator control in the rectum of the cat and its possible mediation by vasoactive intestinal polypeptide.

Vascular and motor responses in the rectum to pelvic nerve stimulation are described in the anaesthetized cat and compared with corresponding effects observed in the colon. The responses comprise a cholinergic and a non-cholinergic component, and an attempt has been made to elucidate the latter. Pelvic nerve stimulation evoked a pronounced and well maintained vasodilator response in the rectum whereas that in the colon was transient. Maximal vasodilatation occurred at much lower stimulus frequencies in the rectum (2-4 Hz) than it did in the colon (8-16 Hz) and maximal blood flow under these conditions was also greater in the rectum (greater than 200 ml 100 g-1 min-1) than the colon (less than 150 ml 100 g-1 min-1). Muscarinic blockade further curtailed the colonic vasodilator response to pelvic nerve stimulation, whereas the rectal dilatation was only slightly reduced in the presence of atropine. Pelvic nerve stimulation caused a substantial release of vasoactive intestinal polypeptide (VIP) from the rectum, which was related both in magnitude and duration to the vasodilatation. Intra-arterial infusions of VIP, which reproduced this rise in rectal venous VIP concentration, caused a rectal vasodilator response which closely resembled that during pelvic nerve stimulation after cholinergic blockade. The rectal vasculature was estimated to be 50-100 times more sensitive to VIP than the colonic vasculature. VIP therefore seems to be the most likely putative neurotransmitter responsible for non-cholinergic rectal vasodilatation. Stimulation of the pelvic nerves also caused rapid contractile motor responses before, and more gradual motor responses after, muscarinic blockade in both the colon and rectum, in the latter preceded by a non-cholinergic relaxation. These patterns of motor activity largely confirm previous results. Infusions of substance P effectively mimicked the non-cholinergic contractile motor responses but failed to demonstrate significant release of this peptide during pelvic nerve stimulation in the present experiments. However, substance P is rapidly inactivated and might possibly be involved in these responses. Stimulation of the pelvic nerves in bursts at high frequencies (up to 80 Hz), simulating a discharge pattern observed electrophysiologically in vivo, was effective in eliciting all the above responses, with the exception of the colonic contraction.

Animals↗

Effects of stimulation of the chorda tympani in bursts on submaxillary responses in the cat.

1. The effects of continuous preganglionic stimulation of the chorda tympani at 2 Hz for 10 min were compared with those of stimulation at 20 Hz in 1 sec bursts at 10 sec intervals for the same period in cats treated with atropine (0.5 mg/kg). Both the fall in mean submaxillary vascular resistance (s.v.r.) and the rise in mean vasoactive intestinal peptide (VIP) output from the gland were increased significantly (P < 0.01; P < 0.02) when the same total number of impulses were delivered in the form of bursts at the higher frequency.2. Both responses were also consistently increased by stimulating the post-ganglionic innervation in bursts in atropinized cats, or by stimulating the preganglionic innervation in bursts in the absence of atropine.3. The effects of stimulation of the chorda tympani in 1 sec bursts at 10 sec intervals for 2-3 min were investigated over the frequency range 2-160 Hz. The change in mean s.v.r. under these conditions was significantly reduced by administration of atropine at frequencies between 2 and 20 Hz, but not at higher frequencies. In atropinized cats, the fall in mean s.v.r. was linearly related to stimulus frequency (r = 0.993) over the range 2-60 Hz and a maximal response was obtained during stimulation at 80 Hz. In the same experiments the fall in mean s.v.r. was linearly related to log mean VIP output over the frequency range 20-160 Hz (r = 0.998).4. Closely similar changes in mean s.v.r occurred in response to both pre- and post-ganglionic stimulation at all frequencies tested between 2 and 160 Hz in atropinized cats when the stimuli were delivered in bursts. The changes in mean s.v.r. were not significantly affected by varying the duration of individual stimuli over the range 0.1-25.0 msec.5. The flow of submaxillary saliva was also linearly related to stimulus frequency over the range 2-40 Hz (r = 0.997) when the stimuli were delivered in bursts in the absence of atropine and secretion of saliva was maximal at 60 Hz.6. It is concluded that release of VIP from the submaxillary gland of the cat is optimal in response to stimulation of the chorda tympani at relatively high frequencies, when the impulses are delivered in bursts. Flow of saliva which is mediated by acetyl choline, may also be potentiated under the same conditions.

Animals↗

Adrenal catecholamine output in response to stimulation of the splanchnic nerve in bursts in the conscious calf.

1. Different patterns of stimulation have been applied to the peripheral end of the right splanchnic nerve, below behavioural threshold, in conscious 2-5 week-old calves. 2. The effects of continuous stimulation at 4 Hz for 10 min were compared with those of stimulation at 40 Hz in 1 s bursts at 10 s intervals for the same period. Delivering the same total number of impulses in the form of bursts in this way increased the output of both adrenaline and noradrenaline and this increase was statistically significant in the case of adrenaline (P less than 0.02) but not noradrenaline. 3. The effects of stimulation in 1 s bursts at 10 s intervals for 2-3 min were investigated over the frequency range 10-150 Hz and compared with the effects of continuous stimulation over the range 1-15 Hz obtained previously in conscious calves of the same age (Edwards, Furness and Halle, 1980). The output of adrenaline but not noradrenaline was found to significantly greater in response to stimulation in bursts at frequencies of up to 40 Hz than when the equivalent number of impulses were delivered at a constant rate (P less than 0.02). 4. It is concluded that the release of catecholamines from the adrenal gland is maximal at relatively high frequencies (40-100 Hz) when the impulses are delivered in bursts.

Adrenal Medulla↗

Effects of the autonomic system on insulin release in response to exogenous glucose in weaned lambs.

1. The role of the autonomic innervation to the pancreas in mediating the release of insulin in response to exogenous glucose has been investigated in conscious weaned lambs 4-5 months after birth. 2. The incremental rise in mean plasma insulin concentration was consistently lower in lambs with cut splanchnic nerves, which had been pre-treated with atropine (0.2 mg kg-1), than in normal control lambs, although the differences did not achieve statistical significance. 3. Pre-treatment with propranolol (0.25 mg kg-1) effectively suppressed release of insulin in response to exogenous glucose in atropinized lambs with intact splanchnic nerves, but not in atropinized lambs with cut splanchnic nerves. 4. The rise in mean plasma insulin concentration was significantly greater in lambs pre-treated with atropine (0.2 mg kg-1) and phentolamine (0.1 mg kg-1 initially, followed by 0.02 mg kg-1 min-1) than in atropinized lambs with cut splanchnic nerves. 5. It is concluded that release of insulin in response to exogenous glucose is normally modified by both sympathetic alpha-adrenergic inhibition and beta-adrenergic excitation in this species.

Animals↗