Biomedical subjects

A V Edwards

Publications and source records attributed to A V Edwards.

At least 37 records · Page 2Linked to original sources

PubMed1997

Role of adrenoceptors in the hypertensive response to feeding in the conscious calf.

Ingestion of milk during suckling causes hypertension and tachycardia in young, unweaned animals of many species, but these responses are most pronounced in the calf. The present study was undertaken to assess the extent to which this phenomenon depends on activation of adrenoceptors in these animals. Mean basal heart rate was 100 +/- 8 beats/min and mean basal aortic blood pressure was 92 +/- 5 mmHg. The rise in heart rate during feeding was almost completely suppressed after propranolol (2-4 mg/kg iv), which also significantly reduced the rise in blood pressure from 67 +/- 4 to 44 +/- 3 mmHg (P < 0.005). Additional pretreatment with phentolamine (1.0 mg/kg and < or =0.1 mg x min(-1) x kg(-1) iv) virtually eliminated the rise in blood pressure during feeding; it rose by only 8 +/- 4 mmHg (P < 0.001). Section of both splanchnic nerves also significantly reduced the rise in blood pressure during feeding, especially after pretreatment with propranolol. Neither section of the splanchnic nerves nor the administration of the blocking agents significantly affected the rises in plasma insulin and pancreatic polypeptide that occurred after feeding. There was no detectable rise in plasma neuropeptide Y concentration in response to feeding. The hypertensive response to direct electrical stimulation of the peripheral end of a splanchnic nerve and to intra-arterial injections of norepinephrine were completely abolished after combined pretreatment with atropine, propranolol, and phentolamine after the ipsilateral adrenal vein had been tied off. It is concluded that the cardiovascular changes that occur during feeding in these animals are attributable very largely, if not entirely, to activation of adrenoceptors.

Adrenergic alpha-Antagonists↗

PubMed1996

Nitric oxide and release of the peptide VIP from parasympathetic terminals in the submandibular gland of the anaesthetized cat.

The role of nitric oxide (NO) in mediating various submandibular responses to stimulation of the parasympathetic innervation has been investigated in anaesthetized cats, in which N omega-nitro-L-arginine methyl ester (L-NAME; 30 mg kg-1 I.A.) was used to block the synthesis of NO. L-NAME significantly reduced the vasodilator response and the flow of saliva, together with the output of salivary protein that occurred during stimulation of the chorda lingual nerve (20 Hz for 1 s at 10 s intervals), without significantly reducing the output of vasoactive intestinal peptide (VIP) from the gland. The results show that NO is implicated not only in the release of VIP, as established previously, but also in mediating its actions following release in the submandibular gland of the cat.

Animals↗

PubMed1995

Presence and effects of pituitary adenylate cyclase activating peptide in the submandibular gland of the ferret.

Pituitary adenylate cyclase activating peptide (PACAP), a recently described vasoactive intestinal peptide-like neuropeptide, was found to be present in neurons in the submandibular gland of the ferret, where PACAP-immunoreactive nerve fibers were distributed around blood vessels, acini and ducts. Most of the PACAP-immunoreactive fibres were distinct from those storing vasoactive intestinal peptide. PACAP occurs in tissues as PACAP1-38 and PACAP1-27. PACAP1-38 and PACAP1-27 but not PACAP16-38 displayed biological activity with about the same potency. They exerted vasodilator effects on the submandibular vasculature, which resulted in a greater fall in vascular resistance than an equimolar dose of vasoactive intestinal peptide. The vasodilator response was independent of muscarinic receptor activation. Neither vasoactive intestinal peptide nor PACAP alone evoked any flow of saliva. However, both vasoactive intestinal peptide and PACAP enhanced the fluid response to acetylcholine, and the flow of saliva as well as the output of protein in response to parasympathetic nerve stimulation, vasoactive intestinal peptide being more potent than PACAP. In vitro, protein was released from submandibular gland tissue in response to both vasoactive intestinal peptide and PACAP, vasoactive intestinal peptide being more potent than PACAP. PACAP (and vasoactive intestinal peptide) exerted its in vitro effect following adrenoceptor and muscarinic blockade and following degeneration of sympathetic nerves. Sympathetic denervation combined with parasympathetic preganglionic denervation resulted in supersensitivity to both vasoactive intestinal peptide and PACAP. The fact that PACAP and vasoactive intestinal peptide occur in different nerve fibre populations suggests different roles for the two peptides in the submandibular gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1995

The role of nitric oxide in the control of protein secretion in the submandibular gland of the cat.

Submandibular salivary responses to stimulation of the parasympathetic chorda lingual innervation have been investigated in anaesthetized cats in the presence and absence of N omega-arginine-L-methyl ester (L-NAME) to block the synthesis of nitric oxide. Stimulation either at 2 Hz continuously or at 20 Hz for 1 s at 10 s intervals produced an abrupt fall in submandibular vascular resistance and initiated a flow of submandibular saliva. Neither of these responses differed significantly from the other but the output of protein was significantly potentiated (P < 0.05) when the high-frequency intermittent pattern of stimulation was employed. This potentiation of protein output was abolished in the presence of L-NAME, when the output of protein from the gland was closely similar, whichever pattern of stimulation was employed. Additional administration of atropine completely blocked all submandibular responses to parasympathetic stimulation showing that, in the presence of L-NAME, each response was due to release of acetylcholine acting on muscarinic receptors. The intermittent pattern of chorda lingual nerve stimulation produced a significant rise in the output of vasoactive intestinal peptide (VIP) from the gland (P < 0.01) and this response was significantly reduced following administration of L-NAME (P < 0.05). The results are consistent with the contention that stimulation of the parasympathetic innervation in bursts, which increases the amount of VIP released from the postganglionic nerve terminals, enhances the output of protein in submandibular saliva in the cat. The mechanism involves nitric oxide (NO), which may act, at least in part, presynaptically by modulating VIP release.

Animals↗

PubMed1994

Muscarinic involvement in vascular and adrenal medullary responses to splanchnic nerve stimulation in conscious calves.

Stimulation of the peripheral end of the right splanchnic nerve (4 Hz for 10 min) in the presence of hexamethonium caused a small but significant rise in mean aortic blood pressure which was subsequently abolished by atropine. There were also small but significant increases in the outputs of catecholamines, [Met5]-enkephalins and corticotrophin releasing factor (CRF) from the right adrenal gland. The catecholamine response was roughly halved after atropine while the outputs of enkephalins and CRF were unaffected. It is concluded that splanchnic sympathetic postganglionic neurones supplying the vasculature are completely blocked by cholinergic blockade whereas adrenal medullary responses persist in an attenuated form.

Adrenal Medulla↗

PubMed1994

Nitric oxide-related pancreatic endocrine responses to hyperglycaemia in the conscious calf.

Mean plasma insulin concentration was reduced and mean plasma glucose concentration increased following the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mumol kg-1 i.a.) in conscious calves given continuous infusions of exogenous glucose (30-60 mumol min-1 kg-1 i.v.). It is concluded that the rise in plasma insulin concentration which occurs in these animals in response to glucose is mediated, at least in part, by a nitric oxide-related factor (NOx).

Animals↗

PubMed1994

Adrenal responses to the peptide PACAP in conscious functionally hypophysectomized calves.

Intra-aortic infusions of pituitary adenylate cyclase-activating peptide-(1-38) (PACAP) produced a dose-related fall in aortic blood pressure over the range of 4-40 pmol.min-1.kg-1 in the presence of exogenous adrenocorticotropic hormone-(1-24) (ACTH, 2 ng.min-1.kg-1 i.v.; P < 0.01). At the higher dose there was a significant fall in adrenal vascular resistance in the absence, but not in the presence, of ACTH. PACAP also produced a dose-related increase in right adrenal cortisol output over the same range, which was significantly greater in the absence of exogenous ACTH (P < 0.01). At the higher dose, PACAP produced small but significant increases in adrenal epinephrine and norepinephrine output (P < 0.01) both in the presence and the absence of ACTH. There was also a small rise in Met5-enkephalin output, and corticotrophin-releasing factor (CRF) was released in the presence, but not in the absence, of ACTH. It is concluded that PACAP is capable of exerting potent steroidogenic and vasodilator effects in the adrenal gland in the normal conscious calf and of releasing significant amounts of catecholamines, enkephalins, and CRF from the adrenal medulla. These findings identify PACAP as a candidate neuromodulator in the adrenal gland in this species.

Adrenal Cortex↗

PubMed1994

Effects of substance P on adrenal responses to acetylcholine in conscious calves.

The effect of intra-aortic infusions of substance P (SP; 10 or 20 pmol.min-1.kg-1) on adrenal responses to acetylcholine (4.5 nmol.min-1.kg-1 ia) have been investigated in functionally hypophysectomized calves given exogenous adrenocorticotropic hormone (0.7 pmol.min-1.kg-1). At the lower dose, SP had no effect on cortisol output. In contrast, SP inhibited the output of both catecholamines and enkephalins in response to acetylcholine, without affecting the output of corticotropin-releasing factor (CRF). Increasing the dose of SP to 20 pmol.min-1.kg-1 ia significantly reduced the outputs of both cortisol and CRF (P < 0.025 and 0.01 respectively). It is concluded that SP is capable of modulating both adrenal cortical and medullary responses to acetylcholine and that the latter are more sensitive to this influence than the former.

Acetylcholine↗

PubMed1994

Pancreatic endocrine responses to substance P and calcitonin gene-related peptide in conscious calves.

Both substance P (SP) and calcitonin gene-related peptide (CGRP; 0.13 micrograms.min-1.kg-1 for 10 min) produced a significant rise in arterial plasma pancreatic polypeptide (PP) concentration, and additive responses were obtained when both peptides were infused simultaneously and/or with acetylcholine (0.7 micrograms.min-1.kg-1 ia). The PP response to SP was abolished by intravenous infusions of glucose, whereas those to CGRP and acetylcholine were not significantly affected. Neither SP nor CGRP had any effect on plasma insulin concentration, either in the presence or absence of exogenous glucose, whether infused singly or together, or in the presence of acetylcholine. SP, but not CGRP, produced a small but statistically significant rise in mean plasma glucagon concentration when infused together with acetylcholine. These results suggest that SP and CGRP may modulate the secretion of PP and glucagon in the normal conscious calf but not that of insulin. It is also possible that SP modulates secretion of pancreatic glucagon in these animals.

Acetylcholine↗

PubMed1993

Nitric oxide-related vasodilator responses to parasympathetic stimulation of the submandibular gland in the cat.

1. The extent to which parasympathetic vasodilator responses, in the submandibular gland of the cat, depend upon release of nitric oxide related (NO chi) or endothelium-derived relaxing factor (EDRF) within the gland has been investigated in anesthetized cats given N omega-nitro-L-arginine methyl ester (L-NAME) which specifically blocks the synthesis of EDRF from arginine. 2. Close intra-arterial infusions of L-NAME (> or = 100 mg kg-1) produced a steady and significant rise in mean aortic pressure together with a steady increase in basal submandibular vascular resistance over the next 20-30 min, which persisted thereafter. 3. In cats pretreated with propranolol, to block beta-adrenoceptor-mediated vasodilatation, salivation and vasodilatation in response to stimulation of the chorda-lingual nerve were reduced but not abolished by L-NAME (> or = 100 mg kg-1, I.A.). Subsequent administration of atropine (> or = 1 mg kg-1 I.V.) completely suppressed the secretory response and virtually eliminated the vascular response. 4. In cats pretreated with atropine (> or = 1.0 mg kg-1 I.V.) administration of L-NAME (> or = 100 mg kg-1 I.A.) effectively suppressed the vasodilator response to chorda-lingual stimulation at 2 Hz continuously, or at 20 Hz for 1 s at 10 s intervals. 5. Administration of L-NAME (> or = 100 mg kg-1 I.A.) effectively suppressed the submandibular vasodilator response to infusions of VIP (10 and 20 ng I.A.) and significantly reduced, but did not abolish that to acetylcholine (100 ng min-1 I.A.). 6. These results provide further support for the view that both acetylcholine and vasoactive intestinal polypeptide-like immunoreactivity (VIP) are released from the postganglionic parasympathetic nerve terminals and produce effects on the blood vessels in submandibular glands of the cat. They also provide evidence for a direct vascular action of acetylcholine, independent of NO chi, but VIP appears to act indirectly via NO chi formation.

Animals↗

PubMed1993

Adrenal cortical and medullary responses to acetylcholine and vasoactive intestinal peptide in conscious calves.

1. Adrenal responses to intra-aortic infusions of acetylcholine and vasoactive intestinal peptide (VIP) have been investigated in functionally hypophysectomized calves given exogenous adrenocorticotrophic hormone (ACTH, 2 ng min-1 kg-1 I.V.). 2. Infusions of VIP at a dose of 0.13 micrograms min-1 kg-1 caused a small, but significant increase in adrenaline and noradrenaline output which was, however, far below the level recorded previously in response to acetylcholine (0.7 micrograms min-1 kg-1). In contrast, these doses of the two agonists produced closely similar rises in adrenal cortisol output. 3. The steroidogenic effects of acetylcholine and VIP were found to be strictly additive and no evidence of potentiation was obtained in relation to either cortical or medullary responses or in the case of any of the cardiovascular responses which were monitored. 4. Intra-aortic infusions of VIP, at a dose which produced a substantial increase in adrenal steroidogenesis (0.065 micrograms min-1 kg-1), had no effect on the output of catecholamines, enkephalin-like immunoreactivity or corticotrophin-releasing factor, either in the presence or absence of acetylcholine. 5. It is concluded that VIP is unlikely to modulate adrenal medullary responses to muscarinic stimulation in this species as it has been claimed to do in the rat and does not potentiate adrenal steroidogenesis in response to acetylcholine as it does to ACTH.

Acetylcholine↗

PubMed1993

Autonomic control of adrenal function.

Recent studies of adrenal function in conscious calves are reviewed. These have involved collecting the whole of the adrenal effluent blood from the right adrenal gland at intervals and, where necessary, prior functional hypophysectomy by destruction of the pituitary stalk under general halothane anaesthesia 3 d previously. The adrenal medulla was found to release numerous neuropeptides, in addition to catecholamines, in response to stimulation of the peripheral end of the right splanchnic nerve, which was carried out below behavioural threshold. Many of these responses were enhanced by stimulating intermittently at a relatively high frequency. Intra-aortic infusions of a relatively low dose of acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal cortex, agonists which either potentiated the steroidogenic response to ACTH or exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via muscarinic receptors. Stimulation of the peripheral end of the right splanchnic nerve strongly potentiated the steroidogenic response to ACTH and there is compelling evidence that the innervation normally plays an important part in cortisol secretion.

Acetylcholine↗

PubMed1992

The role of corticotrophin releasing factor in relation to the neural control of adrenal function in conscious calves.

1. Adrenal responses to intra-aortic infusions of pure synthetic ovine corticotrophin releasing factor (CRF), and to electrical stimulation of the preganglionic sympathetic innervation, have been investigated in functionally hypophysectomized conscious calves, in the presence and absence of a specific CRF antagonist. 2. CRF exerted a substantial steroidogenic effect on the adrenal gland of functionally hypophysectomized calves when infused intra-aortically at a dose (1.3 ng min-1 kg-1) below that which caused any fall in the arterial blood pressure. This response was significantly reduced, but not abolished by a concomitant infusion of CRF-antagonist into the aorta. 3. The steroidogenic effect of CRF was significantly reduced in the presence of exogenous adrenocorticotrophic hormone (ACTH) (2 ng min-1 kg-1, I.V.) and the surviving response was completely abolished by CRF-antagonist. 4. Stimulation of the peripheral end of the splanchnic nerve at 4 Hz in functionally hypophysectomized calves given exogenous ACTH produced a rise in mean adrenal output of the same order of magnitude as did exogenous CRF under the same conditions. The response to splanchnic nerve stimulation was apparently unaffected by CRF-antagonist although release of endogenous CRF from the gland was significantly increased thereby. 5. These results indicate that release of CRF from the adrenal gland during splanchnic nerve stimulation in the calf does not contribute significantly to the steroidogenic response thereto.

Adrenal Glands↗

PubMed1992

Synergism in the autonomic regulation of parotid secretion of protein in sheep.

1. Stimulation of the cervical sympathetic nerve continuously at 2 Hz, or in bursts of 1 s at 20 Hz every 10 s, for 5 min doubled the resting flow of parotid secretion in anaesthetized sheep and increased its concentration of protein. It also caused a significant increase in the concentration of potassium and decreased that of sodium: these latter effects were linearly inversely related. 2. Stimulation of the parotid nerves (the parasympathetic innervation) continuously at 2 Hz increased the flow of parotid secretion over 15-fold which was significantly more than that which occurred in response to stimulation in bursts at 20 Hz. However, the latter pattern of stimulation significantly increased the concentration of protein in the saliva, which was not altered by stimulation at 2 Hz continuously. 3. Simultaneous stimulation of both the parotid and sympathetic nerves at 20 Hz in bursts substantially increased the output of protein from the gland, above that recorded in response to stimulation of either alone, without potentiating either the volume of secretion produced or the outputs of sodium or potassium. 4. The output of protein was also potentiated when both nerves were stimulated simultaneously at 2 Hz continuously but this pattern of stimulation elicited the secretion of a significantly smaller amount of protein. 5. All parotid responses to stimulation of the parotid nerves, either continuously at 2 Hz or in bursts at 20 Hz, were abolished by atropine (greater than or equal to 0.5 mg kg-1 I.V.), as was potentiation of protein secretion during combined stimulation with the sympathetic innervation. 6. Stimulation of the parotid nerves in bursts at a higher frequency (60 Hz for 1 s at 20 s intervals) elicited a sparse flow of parotid saliva in atropinized animals without significant increase in protein output, with or without simultaneous stimulation of the sympathetic innervation. 7. The results of these experiments show that secretion of protein by the parotid gland, in response to stimulation of the parasympathetic innervation, depends on the pattern of stimulation and is potentiated by concomitant stimulation of the sympathetic innervation in anaesthetized sheep.

Animals↗

PubMed1992

Endothelium-derived vasodilator responses to sympathetic stimulation of the submandibular gland in the cat.

1. The extent to which vasodilator responses to electrical stimulation of the sympathetic innervation, in the submandibular gland of the cat, depend upon release of endothelium-derived relaxing factor (EDRF) within the gland has been investigated in anaesthetized cats given N-nitro-L-arginine methyl ester (L-NAME) which specifically blocks the synthesis of EDRF from arginine. 2. Close intra-arterial infusions of L-NAME (> or = 100 mg kg-1) produced a steady and significant rise in mean aortic pressure together with a steady increase in basal submandibular vascular resistance over the next 20-30 min. It also reduced, but failed to abolish, the vasodilatation which occurs during intermittent stimulation of the sympathetic innervation (20 Hz for 1 s at 10 s intervals) together with the after-dilatation which occurs immediately after a period of continuous stimulation of these nerve fibres (2 Hz). 3. In cats pretreated with the beta-blocker propranolol (> or = 1.0 mg kg-1) both vasodilator responses were reduced, but persisted until L-NAME was administered, whereupon both were abolished. 4. It is concluded that release of EDRF within the submandibular gland of the cat contributes to the basal tone of the vasculature and is responsible for the alpha-adrenergic vasodilator responses to stimulation of the sympathetic innervation, but not for the beta-adrenergic vasodilator responses.

Animals↗

PubMed1992

Inhibitory effects of proopiomelanocortin on cortical and medullary activity in the calf adrenal.

The effects of the infusion of ACTH1-24 and proopiomelanocortin on the denervated adrenal gland have been investigated in conscious 3-6 weeks-old calves by means of the adrenal-clamp technique. To prevent variation in the release of endogenous ACTH the pituitary stalk was cauterized during preparatory surgery. ACTH1-24 (5 ng/min per kg, i.v.) increased the output of cortisol from the adrenal by about 500 ng/min per kg body weight and this effect was rapidly reduced by simultaneous infusion of ovine proopiomelanocortin at 5 ng/min per kg. Release of met5-enkephalin and leu-enkephalin from the adrenal was reduced by ACTH1-24 (P less than 0.05) and this effect was enhanced significantly by additional infusion of proopiomelanocortin (P less than 0.02). However met5-enkephalin represented less than one-third of the met-enkephalin containing peptide released and the output of this pool was unaffected by infusion of ACTH. Proopiomelanocortin had no effect on met5-enkephalin production nor that of the total pool of met5-enkephalin containing peptides. It is concluded that ACTH reduced the quantity of pro-enkephalin processed to met5-enkephalin.

Adrenal Cortex↗

PubMed1991

Atropine-resistant submandibular responses to stimulation of the parasympathetic innervation in the anaesthetized ferret.

1. Submandibular salivary and vascular responses to stimulation of the peripheral end of the chorda-lingual nerve at 20 Hz continuously for 60 min were investigated in anaesthetized ferrets, in which the sympathetic innervation to the gland was cut, in the presence and absence of atropine (2.0 mg kg-1). 2. Both the increase in submandibular salivary flow and protein output, which occurred in response to nerve stimulation, were substantially reduced following the administration of atropine, the latency was greatly increased thereby, and both responses were more transient but neither was abolished by atropine. The fall in submandibular vascular resistance was not significantly affected by atropine, either in respect of extent or duration. 3. Chorda-lingual stimulation produced an increase in the output of vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) in the submandibular venous effluent blood. Each of these responses was maximal within the first 10 min after the onset of stimulation and declined thereafter. The time-scales of both the CGRP and SP responses were similar to those of the atropine-resistant secretory responses, both being quite short-lived, whereas the output of VIP (like the atropine-resistant vascular response) was significantly greater than the basal value throughout the whole of the 60 min period of stimulation. 4. The CGRP response was completely abolished by pre-treatment with atropine, whereas the outputs of both VIP and SP were significantly enhanced thereby. Both the submandibular vascular and secretory responses to chorda-lingual stimulation were almost completely suppressed following the administration of hexamethonium, and there was then no detectable release of peptidergic agonists from the gland. 5. The atropine-resistant submandibular salivary secretory responses were completely abolished by pre-treatment with a tachykinin inhibitor [( D-Arg1, D-Cl2 Phe5, Asn6, D-Trp7,9, Nle11]-SP; 0.75 mg kg-1) without affecting the fall in submandibular vascular resistance. 6. Following pre-treatment with hexamethonium, I.V. bolus injections of methacholine, SP and CGRP elicited increases in submandibular blood flow and secretion of saliva. VIP caused an increase in blood flow without overt secretion, although it is known to increase secretion of protein and to potentiate the secretory response to SP. Taken together, all these results are consistent with the contention that VIP contributes to the vasodilator response to stimulation of the para-sympathetic innervation in this gland and that both SP and CGRP are likely to contribute to the secretory response.

Animals↗

PubMed1991

Endocrine responses to intra-aortic infusions of acetylcholine in conscious calves.

1. Adrenal responses to intra-aortic infusions of acetylcholine (4.5 nmol min-1 kg-1 for 10 min) have been investigated in conscious, functionally hypophysectomized, 3- to 6-week-old calves, in the presence and absence of exogenous ACTH (2 ng min-1 kg-1, I.V.). 2. Acetylcholine produced a substantial fall in adrenal vascular resistance, which was significantly reduced in the presence of exogenous ACTH, while producing minimal changes in aortic blood pressure and heart rate. 3. There was also a significant rise in right adrenal cortisol output which was sufficient to produce a measurable rise in plasma cortisol concentration. The effect could be accounted for by the increase in adrenal ACTH presentation. It was abolished by pre-treatment with atropine (0.2 mg kg-1). A small but significant rise in aldosterone output during acetylcholine infusions was also abolished in the presence of ACTH. 4. Both adrenaline and noradrenaline were released during intra-aortic acetylcholine infusions and these responses were substantially reduced, but not abolished, by pre-treatment with atropine. 5. Acetylcholine also stimulated the release of corticotrophin-releasing factor (CRF) and [Met5]enkephalins from the gland. The output of CRF was enhanced and that of free [Met5]enkephalin was significantly reduced in the presence of exogenous ACTH. All these responses were largely, but not completely, suppressed by atropine. 6. Acetylcholine also promoted the release of the pancreatic hormones glucagon, insulin and pancreatic polypeptide (PP). The amounts of pancreatic glucagon and insulin that were released were highly dependent on the concentration of glucose in the circulating plasma and all these responses were abolished by atropine. 7. It is concluded that acetylcholine is capable of stimulating the release of a wide variety of agonists from the adrenal gland when infused intra-aortically at a dose of 4.5 nmol min-1 kg-1. The increase in cortisol output appears to be secondary to an increase in blood flow whereas the adrenal medullary responses are not, and appear to be due largely, but not entirely, to activation of muscarinic receptors.

Acetylcholine↗