Adrenal Catecholamine Secretion Research Articles

Capsaicin‐sensitive sensory neurons are involved in the plasma catecholamine response of rats to selective stressors.

1. The effect of capsaicin pre-treatment on adrenal catecholamine (CA) secretion in response to stress is controversial. In earlier experiments performed under pentobarbitone anaesthesia, the release of CA in response to stress was complicated by the effects of the barbiturate anaesthesia. 2. In the present study we have used conscious freely moving rats with indwelling cannulae to study the effect of neonatal capsaicin pre-treatment on the plasma CA response to different types of stressors (swimming stress, hypovolaemic stress, immobilization stress and cold stress). 3. After swimming for 20 min, plasma noradrenaline (NA) levels increased by 8-fold and adrenaline by 2-fold in control rats. The increase in plasma NA levels in the capsaicin group was attenuated at 10 min of swimming compared with the vehicle group (P < 0.05). 4. With hypovolaemic stress, there were no differences in plasma CA levels, blood pressure and heart rate between the capsaicin group and the vehicle group. There were also no differences in plasma CA levels after immobilization stress between the two groups. 5. With cold stress, plasma NA levels increased 5-fold and adrenaline levels by 3-fold over basal at 45 min in the vehicle pre-treated rats. This increase was not observed in the capsaicin group. 6. Immunoreactive substance P was depleted by only 68% in the splanchnic nerve following capsaicin pre-treatment. If the remaining 32% was biologically active substance P then it could account for the maintenance of the response to hypovolaemic and immobilization stress. However, it might be possible that the responses to hypovolaemic and immobilization stresses could be attenuated if a more complete depletion were achieved. 7. These results in conscious rats indicate that capsaicin-sensitive sensory neurons are required for plasma CA response to selective stressors. They are required for CA output in response to cold stress and to the early phase of swimming stress, but not to hypovolaemic stress and immobilization stress.

Cardiovascular and adrenaline-releasing effects of the 5-HT 1A receptor agonist 8-hydroxy-2-(DI-N-propylamino) tetralin in streptozotocin diabetic rats

The 5-hydroxytryptamine 1A (5-HT 1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been reported to trigger sympathoinhibition, as evidenced by its cardiovascular effects, and adrenal catecholamine secretion. The purpose of this study was to analyze the cardiovascular and adrenaline-releasing effects of 8-OH-DPAT in 1 week streptozotocin diabetic rats. 8-OH-DPAT-induced changes in mean arterial pressure (MAP) and heart rate (HR) were determined directly in anesthetized rats, whilst changes in plasma adrenaline (and plasma corticosterone and glucose) levels were analyzed in conscious rats. Resting blood pressure and heart rate were diminished in diabetics, when compared with controls. These changes were associated with a decrease in body weight and a marked increase in resting plasma glucose levels. Diabetes did not affect MAP response to 8-OH-DPAT, except for a decrease in the amplitude of MAP maximal fall, which was associated with a diminished bradycardic response to 8-OH-DPAT. Blood pressure response to prazosin (0.5 mg/kg) in 8-OH-DPAT-pretreated rats was also diminished in diabetics. Lastly, diabetes prevented the adrenaline-releasing and hyperglycemic effects of 8-OH-DPAT (250 ug/kg).

Thermal nociception potentiates the release of ACTH and norepinephrine by blood loss

Neuroendocrine and autonomic responses were assessed in chloralose-anesthetized cats after nociceptor activation and after acute blood loss, two of the sensory components that accompany injury. Plasma adrenocorticotropic hormone (ACTH), catecholamines (peripheral and adrenal), and cardiovascular responses were examined after corneal thermal stimulation (52 degrees C), after hemorrhage (10 ml/kg), and after simultaneous presentation of these two stimuli. Corneal heat during hemorrhage evoked an exaggerated increase in plasma ACTH (+185 +/- 76 pg/ml, P less than 0.01) and in peripheral plasma norepinephrine (+0.41 +/- 0.11 ng/ml, P less than 0.01) compared with the responses seen after either stimulus alone. A peripheral origin of norepinephrine was indicated, since the adrenal secretion of catecholamines increased similarly after all stimuli. Extracellular levels of norepinephrine, collected by push-pull perfusion, within raphe pallidus increased after corneal heat but not after blood loss and did not reflect the interaction between these two stimuli. Results indicated that physiological stimulation of nociceptive and cardiovascular receptors interact to potentiate the release of ACTH and norepinephrine into peripheral blood, effects that were not predicted from the responses to either sensory input alone.

Substance P has biphasic effects on catecholamine secretion evoked by electrical stimulation of perfused rat adrenal glands in vitro

The adrenal medulla is innervated by the splanchnic nerve which contains substance P-immunoreactive fibres originating in the dorsal root ganglia but whose function in the adrenal medulla is not known. In the present study, we have examined the effect of exogenous substance P on catecholamine secretion and [ 3H]-choline overflow evoked by field stimulation of the perfused rat adrenal gland. Substance P had biphasic effects on catecholamine secretion evoked by field stimulation: at the lower concentrations (10 −7−3 × 10 −6 M), substance P facilitated catecholamine secretion whereas at higher concentrations (3 × 10 −5 M), substance P inhibited catecholamine secretion. The effects of substance P were long-lasting: substance P at all concentrations present during the second of three 6-min stimulations increased catecholamine secretion during the third stimulation. The enhancement of catecholamine secretion by substance P during field stimulation was not blocked by atropine but was substantially blocked by hexamethonium plus atropine. Substance P at all concentrations inhibited the evoked [ 3H]-choline overflow with a maximal inhibition of 60% (at 10 −6 M). In the absence of stimulation, substance P (10 −7−3 × 10 −5 M) had no effect on the basal catecholamine secretion or basal [ 3H]-choline overflow. These results indicate that substance P has modulatory effects on adrenal catecholamine secretion and [ 3H]-choline overflow evoked by electrical stimulation. Presynaptically, substance P inhibits transmitter overflow from cholinergic nerve terminals and post-synaptically substance P has biphasic effects on catecholamine secretion dependent on the substance P concentration. These results suggest a functional role for substance P-containing fibres innervating the adrenal medulla.

Role of capsaicin-sensitive neurons in catecholamine secretion from rat adrenal glands

Sensory fibres innervate the adrenal medulla but their function is not known. In the present study, we have used the sensory neurotoxin capsaicin to evaluate the effect of capsaicin sensitive sensory fibres on catecholamine (CA) secretion from isolated perfused rat adrenal glands. CA secretion in response to 1 and 10 min electrical field stimulation of adrenal nerve terminals was significantly attenuated in the adrenal glands of adult rats pretreated as neonates with capsaicin and was frequency dependent, being more pronounced at the higher frequencies of stimulation (5 to 30 Hz) than at the low (0.3, 1 Hz) frequencies. Perfusion of control rat adrenal glands with capsaicin did not evoke CA secretion, but did increase CA secretion in response to perfusion with nicotine. Perfusion with capsaicin for 30 min (but not for 4 min) reduced the CA secretory response to subsequent nerve stimulation. The results suggest that capsaicin sensitive sensory neurons innervating the adrenal medulla are involved in the regulation of adrenal CA secretion evoked by electrical stimulation of adrenal nerve terminals.

Comparison of the influence of rostral and caudal raphe neurons on the adrenal secretion of catecholamines and on the release of adrenocorticotropin in the cat

Neuroendocrine and autonomic responses were assessed in chloralose-anesthetized cats after chemical stimulation of medial brain-stem regions, including those that influence nociceptive input to the medullary or spinal dorsal horn. Microinjections of l-glutamate (0.5 M, 160 nl) were directed at the following rostral and caudal raphe nuclei: the periaqueductal gray (PAG), the dorsal raphe nucleus (DR), the raphe magnus (RM), and the raphe obscurus/raphe pallidus (Ro/Rpa). Activation of DR neurons evoked a significant increase in the adrenal secretion of epinephrine (+ 2.6 ± 1.1 ng/min, P < 0.01) that returned towards prestimulus values by 6 min, whereas microinjections into other raphe nuclei had no consistent effect. Activation of Ro/Rpa neurons evoked an increase in the plasma concentration of adrenocorticotropin (ACTH, + 47.9 ± 12.3 pg/ml, P < 0.01), whereas microinjections into other raphe nuclei did not affect ACTH. Arterial pressure increased significantly after activation of PAG (+ 7.5 ± 2.1 mm Hg, P < 0.01) or of DR (+ 4.8 ± 2.0 mm Hg, P < 0.05) neurons, whereas heart rate increased significantly ( P < 0.05) after stimulation of cells wi the Ro/Rpa. Glutamate microinjections within the RM, a raphe nucleus that exerts a significant descending influence on nociceptive input to the medullary and to the spinal dorsal horns, had no consistent effect on any measured variable. No evidence was seen to suggest that chemical activation of neurons within raphe nuclei inhibited the adrenal secretion of catecholamines or inhibited the release of ACTH. The results indicated that glutamate activation of neurons within different raphe nuclei evoked non-uniform effects on neuroendocrine and autonomic function. Further, these data suggested that the neural substrate underlying the control of the adrenal secretion of catecholamines and of the release of ACTH in response to activation of raphe neurons is likely distinct from that which contributes to the descending influence on nociceptive input to the medullary and spinal dorsal horn.

GABA A receptor-mediated increase of cytosolic Ca 2+ in isolated bovine adrenal chromaffin cells

We have studied the effects of GABA on cytosolic free Ca 2+ concentration ([Ca 2+] i) as a means of investigating the role of GABA in adrenal catecholamine (CA) secretion. It was demonstrated that GABA caused an elevation of [Ca 2+] i via the GABA A receptor in a concentration-dependent manner, which was well correlated with an increase of 45Ca uptake, an increase of CA release and a depolarization of chromaffin cells assessed with bis-oxonol fluorescence. Since the GABA-induced rise of [Ca 2+] i was absolutely dependent on the presence of extracellular Ca 2+ and partly sensitive to nifedipine, at least one entry route for Ca 2+ facilitated by GABA via a voltage-sensitive Ca 2+ channel was suggested. When extracellular Cl − was lowered, GABA-induced CA release, depolarization, and rise of [Ca 2+] i were all markedly enhanced. It is possible that GABA plays a modulatory role in the regulation of adrenal CA secretion as a facilitatory modulator.

Effect of capsaicin‐sensitive sensory nerves on plasma glucose and catecholamine levels during 2‐deoxyglucose‐induced stress in conscious rats

1. Sensory fibres innervate the adrenal medulla but their function is not known. In this paper we have studied the effect of capsaicin-sensitive sensory fibres on the adrenal catecholamine (CA) response and blood glucose response to 2-deoxyglucose (2-DG)-induced glucopenic stress in conscious rats. 2. 2-DG at 500 mg kg-1 (i.v.) induced a 2.5 fold increase in plasma glucose levels, a 3.5 fold increase in inferior vena caval (i.v.c.) plasma noradrenaline (NA) levels and a 7 fold increase in i.v.c. plasma adrenaline (Ad) levels over 60 min. The hyperglyaemia in response to 2-DG was attenuated by pentolinium and by left splanchnicotomy plus right adrenalectomy. These procedures also caused a complete inhibition of the increase in plasma CA. 3. The hyperglycaemia in response to 2-DG was attenuated by pretreatment of rats with capsaicin as neonates, suggesting that capsaicin-sensitive sensory fibres are required for regulation of plasma glucose in response to glucopenic stress. 4. The increase in i.v.c. plasma CA levels in response to 2-DG during the early phase of glucopenia (first 30 min) in the conscious rats pretreated with capsaicin was the same as in the rats pretreated with vehicle alone. During the later phase of glucopenia (after 45 min), the increase in plasma CA levels in rats pretreated with capsaicin was higher than in the rats pretreated with vehicle alone. 5. In vehicle-pretreated rats and capsaicin-pretreated rats the tissue NA and Ad levels in the adrenal medulla after 8 h of stress were depleted to the same extent. However, tissue CA levels in the capsaicin group recovered faster over 24 h than in the vehicle group. 6. These results indicate that capsaicin-sensitive sensory fibres are not required to maintain adrenal CA secretion during glucopenic stress in the conscious rat but are required for maintenance of blood glucose levels.

Adrenal blood flow and secretory relationships during hypoxia in anesthetized dogs

To evaluate whether hypoxia-induced increases in adrenal cortical (CQ) and medullary (MQ) blood flow (radiolabeled microspheres) occur secondary to hypoxia-induced secretory activity, pentobarbital-anesthetized ventilated dogs were pretreated with dexamethasone (DEX) to prevent adrenocorticotropic hormone (ACTH) and corticosteroid secretory changes or underwent unilateral adrenal denervation to prevent adrenal catecholamine secretory responses. In nonsurgically stressed dogs, DEX completely prevented increases in ACTH or corticosteroid levels during reduction of arterial oxygen content to 8 vol% but had no effect on hypoxia-induced doubling of CQ. In dogs in which adrenal oxygen consumption (VO2) was measured, DEX reduced VO2 by 50% without altering CQ. Unilateral adrenal denervation prevented hypoxia-induced increases in adrenal catecholamine secretion and MQ but had no effect on the CQ response. These results suggest that hypoxia-induced medullary vasodilation is associated with adrenal catecholamine secretory activity but that increases in CQ occur independent of secretory activity and likely represent direct vascular effects of hypoxia.

Partial transection of the ipsilateral cervical spinal cord evokes a sustained increase in the adrenal section of catecholamines in the cat

The importance of cervical spinal pathways on the adrenal secretion of catecholamines was assessed in chloralose-anesthetized cats. Partial transections of the upper cervical spinal cord were made ipsilateral ( n = 21) or contralateral ( n = 10) to the adrenal vein sampling catheter. Ipsilateral cuts evoked an immediate increase in the adrenal secretion of epinephrine that remained elevated at 60 min (+ 89.7 ± 27.0 ng/min, P < 0.001) and increased the epinephrine/norepinephrine secretory ratio from 1.99 ± 0.4 to 5.02 ± 0.6 by 60 min ( P < 0.01) indicating a preferential augmentation of the secretion of epinephrine. The magnitude of the increase in secretion of epinephrine was well correlated with the cross-sectional area of the ipsilateral cut ( r s = 0.681, P < 0.01 ). In contrast, partial transections of similar size made contralateral to the adrenal vein sample evoked significantly smaller increases in the adrenal secretion of epinephrine by 60 min (+ 12.7 ± 4.8 ng/min) and were not correlated with the cross-sectional area of the cut. The region of transection common to those experiments that caused the greatest increase in the secretion of catecholamines included the deep laminae (laminae V–VII) within the central gray matter as well as a portion of the dorsal columns. Transections restricted to the dorsolateral and lateral funiculi caused small and inconsistent changes in the adrenal secretion of catecholamines. Ipsilateral and contralateral cuts evoked similar effects on peripheral concentrations of catecholamines, on plasma adrenocorticotropin and on plasma angiotensin II, suggesting that the facilitatory effect of ipsilateral cuts on the adrenal secretion of catecholamines was not the result of a humoral mechanism. Arterial pressure and heart rate increased equally by 1 min and returned to prestimulus values by 5 min after transections of the ipsilateral or of the contralateral cervical cord. Electrical stimulation of the ipsilateral cervical spinal cord, caudal to the level of transection, decreased the secretion of epinephrine and arterial pressure by 1 min (−30.5 ± 9.0%, P < 0.05) suggesting the presence of an active inhibitory mechanism that persisted after transection. The results indicated that transections of pathways ipsilateral, but not contralateral, to the adrenal medulla that traverse the upper cervical spinal cord evoke a persistent increase in the adrenal secretion of epinephrine, whereas other indices of neuroendocrine or autonomic function do not reflect this tonic influence. The neural mechanism that underlies the apparent tonic inhibition of adrenomedullary function is distributed over a non-compact ipsilateral projection pathway that is not restricted to the dorsolateral or to the lateral funiculi.

Substance P and GABAergic effects on adrenal and autonomic function evoked by microinjections into trigeminal subnucleus caudalis in the cat

To assess the contribution of putative neurotransmitters in mediating changes in adrenal and autonomic function evoked by activation of medullary dorsal horn neurons, microinjections of substance P, bicuculline methiodide, or muscimol were directed at various laminae of trigeminal subnucleus caudalis in the anesthetized cat. Injections of substance P (35.6 pmol) into the superficial layers (lamina I-II) of subnucleus caudalis increased the adrenal secretion of epinephrine (+8.3 ± 2.3ng/min, P < 0.01), arterial pressure (+11 ± 5.3mm Hg, P < 0.01), and heart rate (+19.4 ± 4.9beats/min, P < 0.01) by 1 min, and increased the plasma concentration of adrenocorticotropin (+26 ± 10pg/ml, P < 0.01) by 3 min. Substance P injections into the magnocellular layers (lamina III-IV) or deep magnocellular layers (lamina V-VI) had no significant effects. Microinjections of the GABA A antagonist, bicuculline methiodide (62.4 pmol), into the superficial layers of subnucleus caudalis increased the adrenal secretion of epinephrine (+4.5 ± 3.2ng/min, P < 0.01) by 1 min, whereas injections of the GABA A agonist, muscimol (280 pmol), decreased the secretion (−5.8 ± 2.8ng/min, P < 0.05) by 6 min. Arterial pressure increased after bicuculline (+17.8 ± 8.2mm Hg, P < 0.01) and decreased after muscimol (−6.3 ± 2.9mm Hg, P < 0.01) injections into the superficial layers. Injections of bicuculline or muscimol into the magnocellular layers or into the deep magnocellular layers had no effect on adrenal secretion of catecholamines or on systemic cardiovascular function. Peripheral venous concentrations of adrenocorticotropin were not affected significantly by microinjections of GABAergic agents regardless of the laminar site of injection within subnucleus caudalis. Equivalent volume injections of artificial cerebrospinal fluid into the superficial laminae of subnucleus caudalis had no significant influence on any measured variable. Substance P-evoked changes in the adrenal secretion of epinephrine were not correlated with changes in adrenal venous blood flow, whereas bicuculline- and muscimol-evoked changes in adrenal secretion of catecholamines were positively correlated with changes in adrenal blood flow ( P < 0.01). The results indicate that substance P and GABA contribute significantly to the trigeminal control of adrenal and autonomic function by acting on neurons in the superficial layers of subnucleus caudalis, a brainstem region that processes nociceptive sensory information.

Effects of angiotensin II on cultured, bovine adrenal medullary cells

Primary cultures of bovine adrenal medullary cells have been used to study the effects of angiotensin II on catecholamine secretion and inositol phosphate accumulation. Angiotensin II induced a weak secretion of both adrenaline and noradrenaline, with a threshold of 10–100 pM and a shallow concentration-dependence up to 10 μM. The response was fully dependent on extracellular Ca ++, was partially inhibited by 100 nM nifedipine, was completely blocked by [Sar 1, Ala 8]-angiotensin II (IC 50 5–10 nM) and was unaffected by 0.1 mM hexamethonium. Angiotensin II also increased inositol phosphate accumulation over the range 1 pM-10 μM. Inositol trisphosphate levels increased in a biphasic manner after 15 sec and 1 min exposure to 10 nM angiotensin II, but were not significantly increased at 30 sec or 5, 15 or 30 min stimulation. Inositol bisphosphate was significantly increased after 1 min. Inositol monophosphate levels only increased after 1 min stimulation, but continued to rise during 30 min stimulation. Removal of extracellular Ca ++ or addition of EGTA reduced basal inositol phosphate accumulation but not the ability of angiotensin II to stimulate inositol phosphate accumulation relative to basal. Nifedipine (100 nM) had no effect on basal or angiotensin II-induced inositol phosphate accumulation. The inositol phosphate response to angiotensin II was abolished by 1 μM [Sar 1, Ala 8]-angiotensin II. The results suggest that secretion of adrenal medullary catecholamines can be evoked by angiotensin II, at concentrations that are compatible with a role for circulating angiotensin II or for angiotensin II generated locally within the adrenal medulla. They do not support the suggestion that the secretory actions of angiotensin II on chromaffin cells are mediated by mobilization of intracellular Ca ++ stores.

Adrenergic receptors of adrenal medullary vasculature.

The present study evaluates possible effects of adrenal catecholamines, released by splanchnic nerve stimulation, on adrenal medullary blood flow (MQ) and adrenal catecholamine secretion (CS). Twelve pentobarbital-anesthetized mongrel dogs were subjected to three identical splanchnic nerve stimulations (5 V, 20 Hz, for 3 min) at 30-min intervals, and MQ (radiolabeled microsphere technique) and CS (high-performance liquid chromatography) were measured before and during each nerve stimulation. Animals were assigned to one of three groups and administered either saline, pindolol (1 and 4 mg/kg), or prazosin (1 and 4 mg/kg) before the second and third nerve stimulation, respectively. In the saline control group, each nerve stimulation resulted in similar increases in MQ and CS. Pindolol attenuated nerve stimulation-induced increases in MQ and CS by 50%, but had no effect on medullary catecholamine concentration. Prazosin augmented nerve stimulation-induced MQ, CS, and medullary catecholamine concentration by 35%. These data suggest that adrenal adrenergic receptors modulate elicited CS and mediate changes in adrenal medullary vascular tone.

Hypoxia and hypercapnia increase the sympathoadrenal medullary functions in anesthetized, artificially ventilated rats.

Graded hypoxia (FETO2 14-6%) and hypercapnia (FETCO2 6-10%), which were applied for 45s and 2 min, respectively, to urethane anesthetized and artificially ventilated rats produced an increase in adrenal sympathetic efferent nerve activity in parallel with increases in adrenaline and noradrenaline secretion measured in the adrenal venous effluent. Percentage increases in adrenaline and noradrenaline were almost equal. In rats whose carotid sinus nerves (CSN) were bilaterally cut, hypoxia did not produce any effect on adrenal sympathetic nerve activity or catecholamine secretion. In contrast, excitatory adrenal nerve and catecholamine secretory responses to hypercapnia remained unchanged in CSN denervated rats. After severing a splanchnic nerve whose branches innervated the adrenal gland, while maintaining the resting level of catecholamine secretion by low-frequency stimulation of the peripheral end of the splanchnic nerve, hypoxia did not produce any increase in catecholamine secretion. Hypercapnia (FETCO2 8 and 10%), however, induced catecholamine secretion from denervated adrenal medulla, although the magnitude of the response was significantly lower than that in animals with adrenal nerve intact. It is concluded that hypoxia stimulates the adrenal medulla via the carotid chemoreceptor reflex whereas hypercapnia acts mainly via mechanisms besides carotid chemoreceptors such as central chemoreceptors with some direct stimulatory effect on the adrenal medulla. The functional significance of these dual mechanisms of sympathoadrenal excitation during hypoxia and hypercapnia is discussed.

A differential effect of yohimbine on adrenal and neuronal catecholamine release during bilateral carotid occlusion in the dog

This study reports on the effects of yohimbine and clonidine on the release of adrenal and renal catecholamines (epinephrine, E; norepinephrine, NE; and dopamine, DA) in response to bilateral carotid occlusion (BCO, 3 min) in vagotomized dogs anesthetized with sodium pentobarbital. The model used allowed us to simultaneously compare adrenal catecholamine secretion with neuronal NE release in the kidney. In control dogs, the net output (ng/min/g tissue) of adrenal E (70.5 ± 19.7), NE (22.2 ± 5.9) and DA (2.6 ± 0.8) increased markedly ( P < 0.01) during BCO to a maximum level of 265.1 ± 87.9, 97.4 ± 30.6 and 10.5 ± 3.2, respectively. Similarly, the net output (ng/min/g tissue) of renal NE (0.66 ± 0.06) and DA (0.09 ± 0.02) increased significantly ( P < 0.01) to 1.00 ± 0.11 and 0.15 ± 0.04, respectively. Aortic systolic pressure (mm Hg) (140.8 ± 8.0) and heart rate (beats/min) (162.7 ± 5.1) also increased ( P < 0.01) to 212.5 ± 19.3 179.5 ± 5.4, respectively. In dogs treated with yohimbine (0.3 mg/kg, i.v.), the net increase in adrenal catecholamine output was diminished by approximately 47% ( P < 0.05). In contrast, the net increase in renal NE output was potentiated by 41% ( P < 0.05). The net increase in heart rate was also enhanced significantly ( P < 0.01) in the presence of yohimbine. In dogs receiving clonidine (15 μg/kg, i.v.), the increases in net output of both adrenal and renal catecholamine were abolished. Similarly, pressor and heart rate responses were abolished in the presence of clonidine. The results indicate that yohimbine exerted a differential effect on renal sympathetic nerves (increase) and adrenal medullae (decrease) in modulating catecholamine release in response to BCO, while clonidine abolished both neural NE release and adrenal catecholamine secretion. This study suggests that a presynaptic α 2-adrenoceptor-mediated mechanism, the blockade of which enhances neural NE release at peripheral sympathetic nerve terminals in many tissues, may not be involved in the modulation of adrenal catecholamine secretion during BCO.

Effect of acute and chronic spinal transection on evoked secretion of adrenal medullary catecholamines in the cat

Eight cats were spinally transected at T 3. After an acute (0–5 days) or chronic (15–37 days) period, animals were rendered decerebrate and the effects of visceral (bladder distention) and somatic (sciatic nerve stimulation) stimuli were examined. Epinephrine, norepinephrine and dopamine levels were measured in plasma collected from the left adrenolumbar vein; heart rate and blood pressure were continuously monitored. In chronic animals both visceral and somatic stimuli most frequently evoked prominent increases in blood pressure and the secretion of adrenal medullary catecholamines; the same stimuli caused little change in these parameters in acute animals. These data indicate that a condition similar to the clinical syndrome of autonomic hyperreflexia may be elicited in the chronic spinally transected cat, and that this condition is accompanied by a notable activation of the adrenal medulla.

Adrenal sympathetic efferent nerve and catecholamine secretion excitation caused by capsaicin in rats.

Capsaicin enhances adrenal medullary catecholamine secretion. The participation of the central nervous system on this enhancement by capsaicin was investigated in alpha-chloralose-urethan- or halothane-anesthetized rats. Intravenous administration of capsaicin caused a rapid and marked increase in adrenal sympathetic nerve activity. The nerve activity began to show an increase with the administration of capsaicin at a dosage of 20 micrograms/kg and significantly increased with a dosage of 200 micrograms/kg, i.e., capsaicin was found to cause a dose-dependent increase in adrenal nerve activity. Cholinergic blocking with hexamethonium bromide and atropine sulfate (1 and 5 mg/kg iv, respectively) attenuated the adrenal epinephrine secretion caused by capsaicin. The direct action of capsaicin on adrenal catecholamine secretion was examined using a retrograde perfusion system of left adrenal gland. Up to 8.2 X 10(-5) M capsaicin did not enhance catecholamine secretion from the adrenal gland. These results suggest that the enhancement of physiological catecholamine secretion by capsaicin is mainly through activation of the central nervous system.

Potentiation of evoked adrenal catecholamine release by cyanide: Possible role of calcium

The effect of cyanide on release of catecholamines was evaluated in isolated bovine adrenal glands stimulated with 4 different agonists. Cyanide (0.1 – mM) increased catecholamine release induced by barium or cadmium 2−3-fold. Acetylcholine or potassium induced secretion of adrenal catecholamines was also enhanced by cyanide, but only to the extent of 30–50%. These data suggest that cyanide acts by multiple mechanisms to enhance evoked catecholamine release. The above results may be partly explained by the fact that cyanide inhibited 45Ca efflux from stimulated bovine adrenals. Changes in plasma membrane permeability may be crucial in the alterations of ion flux and evoked catecholamine release caused by cyanide.

Adrenal secretion of catecholamines evoked by chemical stimulation of trigeminal nucleus caudalis in the cat

Microinjections of the neuroexcitatory substance l-glutamate, were made directly into various laminae of trigeminal nucleus caudalis to examine the influence of medullary dorsal horn neurons on the adrenal secretion of catecholamines in the anesthetized cat. Microinjections into the marginal layers (lamina I–II) or into the deep magnocellular portion (lamina V–VI) of nucleus caudalis ipsilateral to the adrenal vein sample evoked a prompt increase in the secretion of epinephrine and a smaller, yet consistent, increase in the secretion of norepinephrine. Injections into the magnocellular layers (lamina III–IV) had no significant effect on secretion of catecholamines. Injections into nucleus caudalis, contralateral to the adrenal vein sample, had no consistent effect on secretion suggesting that the central pathway from nucleus caudalis to the spinal cord for control of adrenal secretion of catecholamines is mainly ipsilateral. Changes in the adrenal secretion of epinephrine were not correlated with changes in adrenal venous blood flow, in arterial pressure or in heart rate. Arterial pressure was transiently increased by l-glutamate injections into the marginal layers, whereas injections into other laminae had no consistent effect. Heart rate increased regardless of the laminar site injection. The results indicate that local excitation of nucleus caudalis, in laminae that contain the majority of nociceptive neurons, evokes a consistent increase in the adrenal secretion of catecholamines, whereas excitation of neurons in laminae that mainly process non-noxious sensory input has no significant effect. It is concluded that secondary trigeminal neurons that contribute to the autonomie responses to noxious trigeminal stimuli have a similar distribution within nucleus caudalis as those that underlie the sensory-discriminative aspects of nociceptive.

Opioids preserve the adrenal medullary response evoked by severe hemorrhage: studies on adrenal catecholamine and met-enkephalin secretion in halothane anesthetized cats.

Possible modulatory effects of mu-, delta-, and kappa-receptor agonists on the concurrent adrenal secretion of catecholamines and met-enkephalin evoked by staged hemorrhage were examined in four groups of cats (n = 5 in each group) anesthetized with halothane (1 MAC). Group I received saline, group II received the mu-agonist sufentanil (25 micrograms/kg i.v., followed by a maintenance infusion), group III received the delta/mu agonist metkephamid (3 mg/kg i.v.), and group IV the kappa agonist U50488H (3.5 mg/kg i.v.). Samples for norepinephrine, epinephrine, dopamine, and met-enkephalin were taken simultaneously from the adrenal vein, femoral vein, and femoral artery at baseline, after drug administration, and after induction of 25% and 50% hemorrhage. In cats receiving saline, 25% hemorrhage resulted in a significant decline in mean arterial blood pressure (MABP) and no change in adrenal secretion. Fifty percent hemorrhage evoked no significant further fall in MABP, but led to prominent increases in adrenal vein hormone levels (norepinephrine, 30-fold; dopamine, 14-fold; and epinephrine, ten-fold) as compared to post-saline values. During the pre-hemorrhage baseline state, administration of sufentanil evoked a significant six- to 20-fold rise in adrenal vein catecholamine and met-enkephalin levels, whereas the administration of metkephamid and U50488H produced no change in adrenal secretion and a decrease in MABP. After 25% and 50% hemorrhage, there was no difference in adrenal vein hormone levels in cats receiving the mu-, delta-, or kappa-agonists compared to those receiving saline. No differences were observed in the different treatment groups with regard to the proportional levels of catecholamines and met-enkephalin in the adrenal vein during the course of the experiment. The authors conclude that opioids are not involved in the regulation of the secretory adrenal medullary response evoked by hemorrhage, and that the systems involved in mediating these cardiovascular reflexes differ pharmacologically from those systems mediating the autonomic response evoked by pain.