Sympathetic nerve activation decreases the release of vasoactive intestinal polypeptide from the feline intestine

The splanchnic nerves to the small intestine were stimulated in anaesthetized cats. Activation of the sympathetic nerves caused vasoconstriction, increased net fluid absorption and decreased release of vasoactive intestinal polypeptide (VIP) in the small intestine. In the colon, parasympathetic nerve stimulation elicited vasodilatation and increased release of VIP. Additional stimulation of the sympathetic lumbar colonic nerves decreased the colonic blood flow and inhibited the release of VIP. These effects of the stimulation of the lumbar colonic nerves were blocked by phentolamine. It is concluded that, in the feline intestine, sympathetic nerve stimulation presynaptically decreased the release of VIP via an alpha-adrenergic mechanism.     

Bulbospinal tryptaminergic neurones

1. The possible role of bulbospinal tryptaminergic neurones in the control of sympathetic activity has been investigated in anaesthetised cats. 2. Depletion of spinal cord stores of 5-hydroxytryptamine was achieved by systemic administration of p-chlorophenylalanine or by intraspinal microinjections of 5,6-dihydroxytryptamine. 3. Blood pressure was little changed by these treatments, neither was the pattern of ongoing activity in sympathetic nerves (arterial pulse rhythmicity and respiratory modulation), the influence of pulmonary afferent nerves on this activity (determined by an airway occlusion technique), the sympatho-inhibitory influence of the carotid sinus baroreceptors, nor the sympatho-inhibitory or -excitatory influences of somatic afferent nerves. 4. Since both p-chlorophenylalanine and 5,6-dihydroxytryptamine treatment caused extensive disruption of the bulbospinal tryptaminergic neurones, it was concluded that these play no significant role in the mediation of the responses tested in anaesthetised cats in the present study.     

Baroreflex control of jejunal blood flow and fluid transport in cats; effects of yohimbine,an α.-adrenergic antagonist

The aim of the study was to test the hypothesis that baroreceptor unloading increases jejunal fluid absorption rate via an α₂-adrenergic effect on electrogenic active transport. In 13 chloralose-anaesthetized cats, the carotid sinus baroreceptors were isolated and perfused with arterial blood, and we studied the effects of a graded decrease in carotid sinus pressure on intestinal vascular resistance, net fluid absorption rate and the potential difference between the intestinal lumen and the peritoneal cavity (PD). Experiments were performed in seven control animals and in six animals pretreated with yohimbine, an α₂-adrenergic antagonist, at a dose of 0.1 mg kg^-I i.v. Yohimbine per se had no significant effects on systemic arterial pressure, intestinal vascular resistance, net fluid absorption rate or PD. In the control animals, baroreceptor unloading induced an increase in systemic arterial pressure, intestinal vascular resistance and net fluid absorption rate, and a decrease in the PD. Yohimbine pretreatment did not significantly affect the systemic blood pressure response to baroreceptor unloading, but abolished the effect on intestinal vascular resistance and PD. After yohimbine treatment, decreases in carotid sinus pressure still enhanced net fluid absorption rate, but this response was observed in a higher range of carotid sinus pressures than in control animals. We conclude that (1) a major component of the increase in jejunal absorption rate during baroreceptor unloading is due to a non-electrogenic mechanism, which may be either active or passive; (2) this component of the response is not blocked by yohimbine at a dose sufficient for an effect on presynaptic α₂-receptors; (3) the absorptive response to baroreceptor unloading is not a phenomenon secondary to the concomitant jejunal vasoconstriction.     

Electrogenic and electroneutral components of the sympathetic effect on fluid absorption in the rat jejunum

The aim of the study was to test the hypothesis that the sympathetic nerves to the jejunum enhance net fluid absorption rate by inhibiting an electrogenic flux of anions into the lumen. The design of the experiments was based on the observation that the effect of catecholamines on electrogenic transport is abolished by yohimbine, an alpha 2 adrenergic antagonist. Net electrogenic transport in jejunal segments of anaesthetized rats was estimated by measurement of the transepithelial potential difference (PD) and short-circuit current (SCC). Net fluid absorption rate was quantified by a gravimetric technique. The sympathetic nerves to the segment were stimulated electrically, both in vitro and in vivo. The effect of sympathetic nerve stimulation on SCC and net fluid transport was determined in the absence and presence of the alpha-adrenergic antagonists phentolamine (a non-selective alpha-adrenergic antagonist), prazosin (a selective alpha 1-antagonist) and yohimbine (a selective alpha 2-antagonist). Sympathetic nerve stimulation decreased PD and SCC and increased net fluid absorption rate. Phentolamine abolished both the electrogenic response and the effect on net fluid absorption rate, without having any significant intrinsic effects on either parameter. Prazosin per se markedly increased net fluid absorption rate, but did not significantly influence the sympathetic effect on SCC or net fluid absorption rate. Yohimbine abolished the electrogenic effect of sympathetic stimulation, and per se increased net fluid absorption rate in innervated but not in denervated segments. In innervated segments, the absorption rate during sympathetic nerve stimulation was similar in controls and yohimbine-treated animals. In denervated segments, yohimbine significantly attenuated the sympathetic response. The results suggest that the sympathetic nerves enhance fluid absorption rate via effects on both electrogenic and electroneutral epithelial transport. These two components of the sympathetic response seem to be mediated by different alpha-receptor mechanisms.     

On the mode of action of the sympathetic fibres on intestinal fluid transport: Evidence for the existence of a glucose-stimulated secretory nervous pathway in the intestinal wall

The effect of sympathetic nerve stimulation or close i. a.infusion of noradrenaline on net fluid transport was investigated on anesthetized cats. In the presence of glucose in the solution perfusing the intestinal lumen the adrenergic mechanisms increased net fluid absorption in normal intestines. Substituting glucose with mannitol in the perfusate abolished this effect of adrenergic stimulation on the net fluid uptake. Furthermore, the effect of noradrenaline on net fluid transport in normal or choleraic intestines was abolished by tetrodotoxin (TTX), a nerve conductivity blocking agent. This suggests that the sympathetic influence is dependent on intraluminal glucose and that noradrenaline exerts its effect mainly via nerves. TTX significantly increased fluid uptake from normal intestines perfused with an isotonic electrolyte solution containing glucose while a considerably smaller effect was seen in intestinal segments perfused with a solution with mannitol. Based on these findings it is proposed that glucose in some way activates intramural nervous reflex(es) in the intestinal wall. According to this hypothesis the enhancement of fluid transport induced by adrenergic stimuli is explained by an inhibition of the glucose-activated nervous secretion     

The effect of nicotinic and muscarinic receptor blockade on cholera toxin induced intestinal secretion in rats and cats

The effects of hexamethonium (cholinergic nicotinic receptor antagonist) and atropine (cholinergic muscarinic receptor antagonist) on cholera toxin induced secretion were investigated in denervated segments of the small intestine of rats and cats. While there was no effect of atropine, hexamethonium markedly inhibited choleraic secretion and turned it into a net fluid absorption in many animals. This observation further strengthens our hypothesis that the enteric nervous system is involved in cholera secretion.     

Reflex adrenergic control of endocrine pancreas evoked by unloading of carotid baroreceptors in cats.

The effects of unloading of the carotid baroreceptors on arterial plasma glucose concentration as well as on portal plasma immunoreactive glucagon (IRG) and insulin (IRI) concentrations were studied in anestethized, vagotomized cats either by sectioning the sinus nerves or by lowering the pressure in the isolated carotid sinuses. Complete elimination of the carotid baroreceptor discharge by cutting the sinus nerves caused an increase in the arterial plasma glucose concentration by 100% and an increase in the portal IRG level by about 200%, whereas the portal IRI concentration decreased to 50% of its basal value. These baroreceptor-induced changes of the plasma IRG and IRI levels seemed to be graded in relation to the drop in carotid blood pressure and they were clearly detectable when the pressure was lowered from 120 to 90 mmHg in the isolated carotid sinus preparation. The described reflex hyperglycemia, hyperglucagonemia and hypoinsulinemia were mediated to the pancreas and liver mainly by the sympatho-adrenal system, since cutting the splanchnic nerves above the adrenal glands abolished the hyperglycemia and hypoinsulinemic responses and markedly depressed the magnitude of the hyperglucagonemic response. In adrenalectomized cats, complete unloading of the baroreceptors evoked both hyperglucagonemia and hypoinsulinemia although the magnitude of the hormonal responses was diminished. In animals where the pancreas and liver were sympathectomized but the adrenal glands left intact, cutting the sinus nerves evoked a doubling of the IRG level and a slight increase in plasma glucose, but no significant change of the IRI level. I.v. infusion of adrenaline (1 microgram/kg X min) or noradrenaline (5 microgram/kg X min) caused pronounced increases in IRG and plasma glucose and a clear-cut reduction of IRI. We conclude that the function of the endocrine pancreas in the cat can be influenced by variations in the blood pressure by means of a reflex control which originates from arterial baroreceptors. This reflex adjustment of the endocrine pancreas is mediated chiefly by two links of the sympatho-adrenal system, namely by catecholamine-release from the adrenal medulla and, more importantly, by a direct adrenergic nerve fibre influence on the alpha- and beta- cells.     

Reflex adrenergic control of endocrine pancreas evoked by unloading of carotid baroreceptors in cats

The effects of unloading of the carotid baroreceptors on arterial plasma glucose concentration as well as on portal plasma immunoreactive glucagon (IRG) and insulin (IRI) concentrations were studied in an-estethized, vagotomized cats either by sectioning the sinus nerves or by lowering the pressure in the isolated carotid sinuses. Complete elimination of the carotid baroreceptor discharge by cutting the sinus nerves caused an increase in the arterial plasma glucose concentration by 100% and an increase in the portal IRG level by about 200%, whereas the portal IRI concentration decreased to 50% of its basal value. These baroreceptor-induced changes of the plasma IRG and IRI levels seemed to be graded in relation to the drop in carotid blood pressure and they were clearly detectable when the pressure was lowered from 120 to 90 mmHg in the isolated carotid sinus preparation. The described reflex hyperglycemia, hyperglucago-nemia and hypoinsulinemia were mediated to the pancreas and liver mainly by the sympatho-adrenal system, since cutting the splanchnic nerves above the adrenal glands abolished the hyperglycemic and hypoinsulinemic responses and markedly depressed the magnitude of the hyperglucagonemic response. In adrenalectomized cats, complete unloading of the baroreceptors evoked both hyperglucagonemia and hypoinsulinemia although the magnitude of the hormonal responses was diminished. In animals where the pancreas and liver were sympathectomized but the adrenal glands left intact, cutting the sinus nerves evoked a doubling of the IRG level and a slight increase in plasma glucose, but no significant change of the IRI level. I.v. infusion of adrenaline (1 γg/kg × min) or noradrenaline (5 γg/kg × min) caused pronounced increases in IRG and plasma glucose and a clear-cut reduction of IRI. We conclude that the function of the endocrine pancreas in the cat can be influenced by variations in the blood pressure by means of a reflex control which originates from arterial baroreceptors. This reflex adjustment of the endocrine pancreas is mediated chiefly by two links of the sympatho-adrenal system, namely by catecholamine-release from the adrenal medulla and, more importantly. by a direct adrenergic nerve fibre influence on the α- and β-cells.     

Effects of carotid occlusion and left atrial stretch on supraoptic neurosecretory cells.

Acute experiments were performed on pentobarbital-anesthetized cats to determine whether atrial and carotid baroreceptors affected the same neurosecretory neurons in the supraoptic nucleus (SON) of the hypothalamus. The osmosensitivity of these neurons was also determined. Eighty-two SON neurons were antidromically identified and 63 of these increased their firing rates during complete occlusion of the right carotid artery. Further testing of these 63 neurons demonstrated that 56 were inhibited by directly stretching the left atrium and 61 were excited by intracarotid injection of hypertonic saline. Left atrial stretch greatly reduced the neuronal response to carotid occlusion. These results show that the activity of the majority of the antidromically identified SON neurons is altered by left atrial and carotid artery receptors as well as changes in plasma osmolality. Results are consistent with the known influence of these receptors on plasma vasopressin.     

The adrenergic nervous control of fluid transport in the small intestine of normotensive and spontaneously hypertensive rats

Intestinal net fluid transport in normotensive Wistar Kyoto rats (WKR) and spontaneously hypertensive rats of the Okamoto strain (SHR) were studied during 'rest', during electrical stimulation of the regional sympathetic fibres as well as after acute denervation and alpha-adrenergic receptor blockade (phentolamine). During 'rest' no statistically significant difference in fluid transport rate could be demonstrated between WKR and SHR. Cutting the left splanchnic nerve, severing the periarterial nerves or giving phentolamine turned net fluid absorption to net fluid secretion in most SHR, whereas fluid absorption was little influenced in WKR by these procedures. Stimulating the left splanchnic nerve (2, 4, 8 Hz) markedly increased net fluid uptake or decreased net fluid secretion in SHR in a frequency-dependent manner. A small effect was seen in WKR at a stimulation rate of 4 Hz. The 'spontaneous' fluid secretion in denervated intestinal segments of SHR was accompanied by a net chloride secretion. Giving hexamethonium i.v. turned net fluid and chloride secretion into water and ion absorption, suggesting that the secretion was evoked by secretory nervous pathways in the enteric nervous system. It is concluded that the 'spontaneous' fluid and electrolyte secretion seen in denervated intestines of SHR is normally 'concealed' by an augmented rate of firing in the regional adrenergic nerve fibres controlling fluid and electrolyte transport. The possible importance of the 'spontaneous' intestinal secretion in SHR in the pathophysiology of arterial hypertension is tentatively discussed.     

The importance of nervous and humoral factors in the control of vascular resistance, blood flow distribution and net fluid absorption in the cat small intestine during hemorrhage

The influence of preganglionic (splanchnic) and postganglionic (periarterial) denervation of the cat small intestine on the changes in blood flow and net fluid absorption elicited by hemorrhage was investigated. The compiled data from a previous report indicate that hemorrhage induces a vasoconstriction and a redistribution of blood flow towards the absorptive part of the mucosa. The vasoconstriction was unaffected by a total postganglionic denervation whereas after a preganglionic denervation both the vasoconstriction and the redistribution of blood flow were abolished. We have also shown earlier that hemorrhage induced an increase in net fluid absorption as long as no ischemic mucosal lesions developed. This increase was reduced by postganglionic denervation, and was reversed into a small decrease after preganglionic denervation. On the basis of these findings it is proposed that the increase in vascular resistance, the redistribution of blood flow towards the absorptive part of the mucosa as well as the increase in net fluid absorption observed after hemorrhage all are effects mainly mediated via the splanchnic nerves. Furthermore, humoral factors are of major importance for the increase in vascular resistance observed after hemorrhage. The increase in net fluid absorption was shown to be induced both by direct nervous and by humoral factors.     

Reflex Plasma Hyperglycemia and Hyperosmolality Evoked by Unloading of the Carotid Baroreceptors

Hemorrhage is usually accompanied by a considerable increase in the plasma osmolality and glucose concentration due to an augmented release of glucose from the liver. In the present cat experiments an attempt was made to investigate the possible role of different vascular receptors in mediating this hyperglycemic (hyperosmolar) response. Bilateral vagotomy or stimulation of the carotid chemoreceptors by perfusion of the carotid sinus with venous blood at normal pressure only slightly increased the arterial plasma glucose concentration. On the other hand, when the sinus nerves were cut in the vagotomized animal, thereby simulating complete unloading of the carotid baroreceptors, the arterial plasma glucose concentration rose by about 8 mM/L and the arterial plasma osmolality by about 10 mOsm/kg H₂O. Perfusion of the carotid baroreceptors with arterial blood at different levels of hypotension showed that the baroreceptor-induced hyperglycemia was graded in relation to the pressure level. Regional hypotension of the liver, pancreas, intestine, kidneys or brain did not significantly affect plasma glucose concentration or osmolality. We conclude that the reflex release of glucose from the liver during hemorrhage mainly is initiated from the unloading of arterial baroreceptors.     

Contrasting reflex influences of cardiac afferent nerves during coronary occlusion

Afferent neurons contained within cardiac sympathetic nerves may have important influences on the circulation when activated during myocardial ischemia. Although such activation is known to reflexly excite upper thoracic sympathetic efferent neurons, effects on other components of sympathetic outflow are unknown. Therefore, cardiac sympathetic afferent nerves were stimulated by occlusion of coronary arteries to investigate their reflex influences on renal sympathetic nerve activity and systemic arterial blood pressure. Responses were observed in anesthetized cats in which sympathetic and/or vagal cardiac afferent nerves remained intact and arterial baroreceptors remained intact or had been denervated. Stimulating sympathetic afferent neurons caused excitation of renal nerve activity, which was accompanied by variable changes in arterial pressure. Stimulation of vagal afferents by coronary occlusion consistently produced inhibition of renal nerve activity and marked depressor responses. When both components of cardiac innervation remained intact, increases or decreases in renal nerve activity and blood pressure were elicited by coronary artery occlusion in the presence or absence of arterial baroreceptors. These results illustrate that cardiac sympathetic afferent nerves can contribute significantly to cardiovascular control during myocardial ischemia.     

Interaction between antisecretory opioid and sympathetic mechanisms in the rat small intestine

The putative existence of an endogenous opioid antisecretory mechanism in the small intestine was tested in anaesthetized Sprague-Dawley rats. Cholera secretion was elicited with cholera toxin and net fluid secretion was measured in vivo using a gravimetric technique allowing on line registrations. Opioid blockade with naloxone (10 mg kg-1 i.v.) increased the cholera secretion significantly but had no effect on control absorption. Pretreatment with phentolamine (2 mg kg-1 i.v.) eliminated the effect of opioid blockade indicating an interaction between the opioid and the adrenergic mechanisms. The effect of naloxone on cholera secretion was unchanged after acute division of the sympathetic nerves to the intestine and removal of the adrenals. Chronic sympathetic denervation of the small intestine, on the other hand, abolished the effect of opiate blockade on the secretion. The antisecretory effect of sympathetic nerve stimulation was unchanged by opiate blockade. Conclusion: An intrinsic antisecretory opioid mechanism has been demonstrated in the small intestine of the rat. This endogenous opioid mechanism seems to decrease secretion indirectly via peripheral activation of the sympathetic antisecretory system.     

Inferior cardiac nerve activity in the cat during occlusion of the mesenteric artery.

A number of studies in this and other laboratories using hemodynamic and pharmacologic evidence have suggested that occlusion of the mesenteric artery evokes a pressor reflex initiated by mesenteric baroreceptors. To provide additional evidence in support of this hypothesis, neurophysiological recordings were made of inferior cardiac nerve activity during mesenteric artery occlusion (MAO). The results indicate that MAO enhances inferior cardiac nerve activity in the cat, providing that the carotid sinus nerves have been cut. Cutting of the mesenteric nerves further facilitates cardiac nerve activity and abolishes the response to mesenteric artery occlusion. The evidence suggests that MAO evokes a reflex sympathetic discharge which is subject to override by the carotid sinus depressor reflex. The afferent limb of the reflex is characterized by a tonic depressor outflow from the mesenteric pressure receptors.     

Antisecretory effect of splanchnic nerve stimulation on choleratoxin-induced secretion in the cat, an effect mediated at the crypts

The experiments were performed on cats anaesthetized with alpha-chloralose. Segments of the small intestine were perfused with sodium-free hypotonic choline-mannitol solution and intestinal net fluid transport was recorded with a volumetric technique. The content of sodium and chloride in the lamina propria of the small intestinal villus was measured with an electron microprobe in freeze-dried paraffin embedded tissue. In absorbing control intestine, there was an even distribution of electrolytes along the villi. Sympathetic nerve stimulation (5 Hz, 5 ms, 5 V) did not significantly affect electrolyte distribution and net fluid transport. Intestinal secretion was elicited by pretreatment of the intestine with cholera toxin. The concentration of sodium and chloride was elevated in the apical third of the villi in intestines during the secretion since secreted sodium from the crypts was reabsorbed into the villi. Sympathetic nerve stimulation decreased the cholera secretion significantly in intestines pretreated with cholera-toxin. Furthermore, the apical gradients of sodium and chloride in the villi, caused by the reabsorbed sodium and chloride, disappeared during sympathetic nerve stimulation. It is concluded that, in the used experimental model, the antisecretory effect of sympathetic nerve stimulation was caused by inhibition of crypt secretion and not by augmented villus absorption.     

The effect of vagal nerve stimulation on net fluid transport in the small intestine of the cat

The effect of electrical vagal nerve stimulation on intestinal net fluid transport rate was studied in the small intestine of the cat. The splanchnic nerves were severed in all experiments. Absorption was quantified with a new gravimetric technique which made it possible to study fluid transport also during intestinal motility. The stimulation characteristics were varied to activate selectively low threshold fibres or low and high threshold fibres. The observations did not reveal any affects of low threshold stimulation on intestinal fluid transport whereas an inhibition was seen when also the high threshold fibres were stimulated. This inhibitory vagal mechanism could also be elicited after the administration of atropine. Atropine in itself increased “resting” net fluid absorption. The results speak against a role for vagal cholinergic mechanisms in the control of net fluid absorption. There seem, however, to be tonically active intramural cholinergic pathways and noncho-linergic inhibitory vagal neurons of unknown physiological significance.     

The effect of stimulating somatic afferents on cholera secretion in the rat small intestine

The effect on rate of cholera secretion in the small bowel of activation of the group III and A delta afferent fibres in the sciatic nerve was studied in rats. Activation of these fibres at 3 Hz for 60 min significantly diminished choleraic secretion from 121 ± 29 to 25 ± 9 μl × min^-1× 100 cm^-2 serosal surface (mean ±SE; n=9). The effect was apparent after the nerve stimulation. Stimulation of the sciatic nerve had no significant effect on choleraic fluid secretion after interrupting the autonomic nerves to the intestine, nor did it significantly alter net fluid transport in non-choleraic intestine with intact nervous supply. It is proposed that the observations may explain the clinical reports of an effect of acupuncture on cholera secretion.     

The effect of baroreceptors on the latency of evoked responses in sympathetic nerves during the cardiac cycle

1. A rapid increase in pressure in a vascularly isolated perfused carotid sinus has been shown to inhibit a reflex response in efferent sympathetic nerves of the dog evoked by electrical stimulation of the radial nerve.2. In intact preparations with the carotid baroreceptors innervated, the mean latency and the variance of the latency of reflex sympathetic nerve responses was reduced when the stimuli evoking the responses were applied at one point of both cardiac and respiratory cycles. When the baroreceptors were denervated there were no significant differences in the responses to random and synchronized stimuli.3. In intact preparations the latency of evoked responses in sympathetic nerves was found to vary progressively during a cardiac cycle; the maximum increase in latency was observed with the responses that occurred at that phase of the cardiac cycle when the baroreceptors exert maximal inhibition on spontaneous sympathetic activity. After denervation of the carotid sinuses a much smaller change during the cardiac cycle was still present, possibly due to effects produced by baroreceptors of the aortic arch and elsewhere.4. It was concluded that changes in baroreceptor activity, due to beat to beat fluctuations of the systemic arterial pressure are a major factor causing variations in the latency of responses in sympathetic nerves evoked by stimuli applied to a cutaneous nerve.     

The contribution of the arterial chemoreceptors to the stimulation of respiration by adrenaline and noradrenaline in the cat

1. Intravenous infusions of adrenaline and noradrenaline in doses averaging 0.8 mug/kg.min increased the respiratory minute volume of anaesthetized cats breathing room air. The mean increase in respiratory minute volume was 14% during adrenaline infusion and 8% during noradrenaline infusion.2. In a small group of decerebrate cats infusions of adrenaline and noradrenaline increased ventilation by 19 and 27% respectively.3. Intravenous catecholamine infusions also increased the respiratory responses of anaesthetized animals to the inhalation of 5% or 10% O(2) in N(2) and to the inhalation of 5% CO(2) in air.4. Adrenaline and noradrenaline infusions had no significant effect on the ventilation of animals breathing 100% O(2), nor did they significantly alter the respiratory response to the inhalation of 5% CO(2) in O(2).5. After section of the carotid sinus and aortic nerves, a blood-pressure compensator being used to minimize changes in arterial pressure, catecholamines had no effect on the respiration of cats breathing air.6. An increase in carotid body chemoreceptor discharge accompanied the increase in ventilation during catecholamine infusion.7. Intravenous catecholamine infusions still produced an increase in ventilation and carotid body chemoreceptor discharge after both aortic nerves and both cervical sympathetic nerves had been cut.8. Intra-arterial infusions into one carotid artery of 0.2 mug/kg.min of adrenaline or 0.1 mug/kg.min of noradrenaline led to mean increases in respiratory minute volume of 9.9 and 11.5% respectively. No increase occurred after section of the corresponding carotid sinus nerve. Such infusions also evoked an increase in carotid body chemoreceptor discharge.9. It is concluded that the hyperpnoea produced by adrenaline and noradrenaline infusions in the cat is predominantly reflex in origin and is mediated by the arterial chemoreceptors.10. The increase in ventilation produced by adrenaline appears to have a component additional to its effect upon the chemoreceptors though the nature of this action has not been identified.