Epinephrine Output Research Articles

Selective hypoglycemia in the liver induces adrenomedullary counterregulatory response.

The present study was designed to investigate adrenal medullary responses to a selective regional hypoglycemia in the liver of dogs with hepatic cross-perfusion. The liver of recipient dogs (Rc) was perfused with vena caval and aortic blood of donor dogs (Dn) through the portal vein and hepatic artery, respectively. Total hepatic venous blood of Rc was returned to Dn through the left jugular vein. Upon the cross-perfusion, glucose (Glc, 5%) was infused at an average rate of 3.5 +/- 0.2 mg.kg-1.min-1 (n = 12) in Rc to compensate the loss of hepatic Glc delivery into the systemic circulation. Insulin (5.0 IU/kg i.v.) was administered to Dn followed by infusion with an average rate of 0.95 +/- 0.17 IU kg-1.min-1 (n = 6), and this served as the hepatic hypoglycemic group. Saline was similarly administered to Dn, which served as the normoglycemic control group. In the hepatic hypoglycemic group, aortic and vena caval Glc levels in Dn, which represent Glc concentrations entering the liver of Rc, decreased from 129.9 +/- 7.1 and 122.5 +/- 7.8 to 44.6 +/- 6.1 and 38.0 +/- 5.9 mg/dl (P < 0.05) 45 min after insulin administration, respectively. During this regional hepatic hypoglycemia in Rc, the systemic glycemia being kept within a normal range, adrenal epinephrine and norepinephrine output increased from 245.5 +/- 55.8 and 39.1 +/- 9.9 to 618.9 +/- 180.4 and 134.3 +/- 52.7 ng/min (P < 0.05), respectively. By contrast, aortic Glc and insulin levels in Dn of the normoglycemic control group remained unchanged, as did adrenal epinephrine and norepinephrine output in Rc. The results indicate that the regional hepatic hypoglycemia can significantly increase adrenal catecholamine secretion even during systemic (central) normoglycemia. The study suggests that the hepatoadrenal Glc counter-regulatory reflex may be functionally implicated in insulin-induced hypoglycemia.

Adaptation of circadian corticosterone and catecholamine rhythms to light-dark cycle reversal in the rat.

Circadian rhythms of urinary excretion of corticosterone and catecholamines were examined in the rat before and after phase reversal of a 12-hour light and 12-hour dark cycle. After the reversal, the acrophase of rhythm was delayed and became constant again on the 6th day for corticosterone and on the 7th or 8th day for adrenaline. The ratios of light-period output to 24-hour output of adrenaline and noradrenaline, however, adjusted to the new light-dark cycle on 10th day, whereas this ratio became constant on 6th day for corticosterone. Thus, circadian corticosterone rhythm seems to adapt to light-dark reversal more quickly than catecholamine rhythm.

Impact of gestational age on the catecholamine responses of the fetal sheep adrenal to cholinergic stimulation in vitro.

We have used the retrograde perfused adrenal preparation to investigate the catecholamine responses of the fetal sheep adrenal to increasing doses of acetylcholine (ACh) and excess potassium. Adrenal glands were collected from fetal sheep between 84 and 99 days gestation (before innervation; n = 7), between 103 and 113 days gestation (during innervation; n = 8) and between 137 and 144 days (after innervation; n = 9). Whilst the basal output of noradrenaline (NA) did not change between 84 and 144 days gestation, there was a significant increase in the adrenal output of adrenaline (Adr) between 84 and 144 days. The NA response to submaximal doses of ACh (10-10(3) microM) was significantly greater (P < 0.05) between 84 and 99 days gestation (mean NA response: 49.6 +/- 11.4 nmol/(30 min)) than after 137 days gestation (mean NA response: 27.3 +/- 8.3 nmol/(30 min)). Similarly, when the NA response to 10-10(3) microM ACh was expressed as a proportion of the maximal NA response to 10(4) microM ACh, the proportional NA response was greater at 84-99 days (48.9 +/- 11.3% of maximal) than at 137-144 days gestation (27.2 +/- 8.3%). The adrenal NA and Adr responses to 10(3) microM ACh between 84 and 137 days were reduced by up to 99% after the addition of hexamethonium. It appears, therefore, that the fetal adrenal is responsive to ACh before the development of innervation of the gland. There is also a decrease in sensitivity of the NA-secreting cells to submaximal doses of ACh as gestation progresses, which is not associated with a decrease in the size of the releasable pool of NA in the fetal adrenal. We speculate, therefore, that innervation of the fetal adrenal may be associated with an increase in the excitation threshold of the NA cells to nicotinic stimulation.

Patterns of cortisol and adrenaline variation in Australian aboriginal communities of the Kimberley region.

Urinary cortisol and adrenaline excretion rates were measured in three Australian Aboriginal communities in the Kimberley region in the north-west of the country. The three communities, Derby, Kalumburu and Kupungarri, differ in size and remoteness and some lifestyle parameters. Cortisol excretion rate is associated with age and urine flow rate, but there is no association with smoking or the consumption of alcohol. All three communities show very high cortisol excretion rates compared to a sample of UK (Oxford) residents and there are also differences between the three communities. Adrenaline excretion rate also shows associations with age and urine flow rate, but not with smoking. Aboriginal people in the Kimberley region excrete adrenaline at a slightly higher rate than that found in Oxford, which itself is high by world standards. There are no marked differences between communities in their adrenaline excretion rates. Alcohol drinkers in Derby, where alcohol is freely available, have higher adrenaline output than non-drinkers.

Effects of protein kinase C activator and inhibitor on adrenal catecholamine release in response to splanchnic nerve stimulation in anesthetized dogs.

Effects of protein kinase C (PKC) activator and inhibitors on adrenal catecholamine release were examined in anesthetized dogs. Output of epinephrine (EPI) and norepinephrine (NE) was determined from adrenal venous blood by high-performance liquid chromatography (HPLC) with electrochemical detection. All drugs were infused intraarterially (i.a.) into the adrenal gland through the phrenic abdominal artery. Infusion of the PKC activator phorbol-12,13-dibutyrate (PDB 0.1 micrograms/min) increased EPI and NE output during basal state and enhanced increases in catecholamine output induced by splanchnic nerve stimulation (SNS 1 and 3 Hz). These effects of PDB were abolished by the PKC inhibitor staurosporine (SSP 0.3 microgram/min), when both drugs were infused simultaneously. Infusion of SSP (0.1, 0.3, and 1 micrograms/min) caused a dose-dependent inhibition of the SNS-induced increases in EPI and NE output. SNS-induced increases in catecholamine output were also inhibited by another PKC inhibitor polymyxin B (PMB 0.1, 0.3, and 1 micrograms/min) and by the phospholipase C (PLC) inhibitor neomycin (NM 0.3, 1, and 3 mg/min). SSP, PMB, and NM did not affect basal output of EPI and NE. These results suggest that activation of PKC promotes release of adrenal catecholamines and provide indirect evidence that activation of PKC and PLC may be involved in SNS-induced release of catecholamines from dog adrenal gland.

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 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.

Inhibition by nifedipine of endothelin-induced adrenal catecholamine secretion in anesthetized dogs.

The present study was conducted to investigate local effects of endothelin-1 (ET-1) on basal adrenal catecholamine (CA) secretion and underlying mechanisms of action of ET-1 in anesthetized dogs. ET-1 was locally administered to the left adrenal gland through a catheter inserted into the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by an HPLC-electrochemical method. The local infusions (1 min, 0.5 mL/min) of ET-1, in doses of 0.01, 0.1, and 1.0 microgram/mL, resulted in a dose-dependent increase in epinephrine secretion, rising from an initial basal value of 6.9 +/- 1.4 ng.min-1 x g-1 to maximum values of 7.6 +/- 1.5, 81.1 +/- 38.3*, and 680.9 +/- 107.6* ng.min-1 x g-1 (*p < 0.05, n = 7), respectively. Neither mean arterial pressure nor plasma CA levels in aortic blood altered following ET-1 infusions. A similar dose-dependent increase in norepinephrine output was also observed with ET-1. Following the initial peak observed during infusion with the highest dose of ET-1, the output of both epinephrine and norepinephrine remained significantly elevated over a period of 30 min. This ET-1-induced, long-lasting increase in adrenal CA output was abolished by nifedipine (100 micrograms/mL) similarly administered 10 min before ET-1 infusion. The results indicate that ET-1 directly enhances the basal secretion of CA from dog adrenal medulla in vivo. The study suggests that the ET-1-induced increase in adrenal CA secretion is, at least in part, mediated by the opening of dihydropyridine-sensitive L-type calcium channels at the level of adrenal medullary chromaffin cells.

Hepatic extraction and hepatic action of insulin, glucagon, and epinephrine in bivascularly perfused rat liver.

Using a bivascularly perfused rat liver, we investigated the hepatic extraction and hepatic action on glucose output of insulin, glucagon, and epinephrine. The liver was perfused for 70 min without recirculation via the portal vein and hepatic artery (3.0 ml/(min.g liver) from portal vein and 1.0 ml/(min.g liver) from celiac artery). Low and high concentration of insulin, glucagon, or epinephrine (450 and 4,500 pM, 21.5 and 215 pM, or 410 and 4,100 pM, respectively) was added to the perfusing medium via portal vein (P-liver), via celiac artery (H-liver), or via portal vein and celiac artery (H-P-liver). Hepatic extraction of insulin, glucagon, or epinephrine was not significantly different among H- (56 +/- 9 and 21 +/- 5%, 31 +/- 7 and 24 +/- 6%, or 22 +/- 8 and 17 +/- 5%), P- (50 +/- 10 and 23 +/- 6%, 32 +/- 9 and 23 +/- 7%, or 22 +/- 9 and 18 +/- 6%), and H-P-liver (55 +/- 11 and 24 +/- 6%, 30 +/- 9 and 26 +/- 8%, or 20 +/- 9 and 17 +/- 6%). Glucagon- or epinephrine-induced increase in glucose output was also similar in H- (245 +/- 47 and 498 +/- 82 mumol/30 min, or 112 +/- 21 and 215 +/- 38 mumol/30 min), P- (258 +/- 51 and 512 +/- 95 mumol/30 min, or 128 +/- 20 and 220 +/- 36 mumol/30 min), and H-P-liver (263 +/- 58 and 515 +/- 94 mumol/30 min, or 129 +/- 22 and 225 +/- 39 mumol/30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of pirenzepine and hexamethonium on adrenal catecholamine release in responses to endogenous and exogenous acetylcholine in anesthetized dogs.

We investigated the way in which hexamethonium and pirenzepine, a selective muscarinic (M) 1 receptor antagonist, modify the release of catecholamines from dog adrenal gland in response to endogenous and exogenous acetylcholine (ACh) in vivo. Output of epinephrine (EPI), and norepinephrine (NE) was determined from adrenal venous blood by high-performance liquid chromatography (HPLC) with electrochemical detection. Intraarterial (i.a.) injections of ACh (1.5 and 3 micrograms) or muscarine (3 and 6 micrograms) into the phrenicoabdominal artery and splanchnic nerve stimulation (SNS, 3 Hz) produced marked increases in EPI and NE output. Hexamethonium (1 mg/kg intravenously, i.v.) inhibited the increases in EPI and NE output in response to exogenous ACh and SNS. Pirenzepine (10 micrograms/kg i.v.) inhibited the ACh-induced increases in EPI and NE output but did not modify the SNS-induced increases. The muscarine-induced increases in EPI and NE output were also inhibited by pirenzepine. These results indicate that the exogenous ACh-induced release of adrenal catecholamines is mediated through both nicotinic and M1 receptors, in contrast to the predominant mediation of nicotinic receptors in response to endogenous ACh.

Coexisting dysregulations of both the sympathoadrenal system and hypothalamic-pituitary-adrenal-axis in melancholia

In order to delineate putatively coexisting dysregulations between sympathoadrenal system and hypothalamic-pituitary-adrenal (HPA)-axis during depression, the authors measured the following: the pre and postdexamethasone (1 mg) 24 hr urine excretion of noradrenaline, dopamine, adrenaline, 3-methoxy-4-hydroxyphenylglycol (MHPG), free cortisol (UFC), and plasma cortisol. Melancholic patients were characterized by a significantly higher excretion of noradrenaline, dopamine and adrenaline, combined with significantly increased UFC, postdexamethasone plasma cortisol, and UFC values. We found significant and positive correlations between UFC on the one hand, and the 24hr urine excretion of noradrenaline, dopamine, and adrenaline, on the other. By the same token, we established significant relationships between the 24 hr urine excretion of those catecholamines and the postdexamethasone UFC and plasma cortisol values. Cortisol nonsuppressors exhibited a significantly higher excretion of noradrenaline, dopamine and adrenaline, as compared with cortisol suppressors. Dexamethasone administration did not have a significant effect on the urinary output of noradrenaline, dopamine, adrenaline or MHPG.

Surreptitious Self-administration of Epinephrine Resulting in 'Pheochromocytoma'

SELECTED CASE A 35-YEAR-OLD woman with a possible pheochromocytoma was referred to the National Institutes of Health (NIH) from Pittsburgh, Pa. Her symptoms started in December 1987, when she developed headache, tremor, tachycardia, and mild hypertension after an injection of novocaine and epinephrine. Soon the episodes began to occur spontaneously. She often went to a local emergency department, where her blood pressure was as high as 160/100 mm Hg and her heart rate as high as 140 beats per minute. Her urinary epinephrine output was 1600 nmol/d (normal,

Simultaneous evaluation of medullary secretory functions of normal and acutely denervated adrenals

Adrenal medullary secretory function of the right innervated gland was simultaneously compared with that of contralateral acutely denervated gland in anesthetized dogs. During bilateral carotid artery occlusion (BCO), output (in ng/min) from right innervated gland of epinephrine and norepinephrine increased from 86.6 +/- 33.0 and 34.4 +/- 15.1 to 280.8 +/- 86.7 (P less than 0.01, n = 7) and 104.4 +/- 40.6 (P less than 0.01, n = 7), respectively. By contrast, epinephrine output from left denervated gland increased only slightly (P less than 0.05), and norepinephrine did not increase significantly. Net catecholamine output from left denervated gland was markedly attenuated by approximately 90% (P less than 0.01, n = 7) compared with that from right innervated gland. During BCO in the second group of dogs, catecholamine output from sham-denervated left gland increased significantly (P less than 0.01, n = 7) to an extent slightly lower than that observed in right innervated gland. In the third group, intravenous injections of dimethylphenylpiperazinium (5 and 15 micrograms/kg) resulted in a dose-dependent increase (P less than 0.05, n = 7) in catecholamine output from both right innervated and left denervated gland. The results indicate that the present procedure of acute surgical adrenal denervation can eliminate the centrally mediated adrenal response, whereas the medullary secretory response to blood-borne substances remains intact. This model may be a useful tool for studying neuronal and humoral medullary secretory functions in vivo under various experimentally induced stress conditions.

Effect of Chronic Treatment with Clonidine and Spironolactone on Cold-Induced Elevation of Blood Pressure

The present study was designed to determine whether antihypertensive agents known to affect the renin-angiotensin-aldosterone (RAA) system might affect the elevation of blood pressure induced by chronic exposure to cold. Spironolactone, a mineralocorticoid receptor blocker, was added to the food and administered to rats chronically exposed to cold. In addition, clonidine, and alpha 2-adrenergic agonist and inhibitor of renin secretion, was administered to another group of cold-exposed rats by daily intraperitoneal injection. A warm-adapted and a cold-treated control group were also used. Chronic administration of spironolactone prevented the development of hypertension but failed to prevent other adaptive physiological changes characteristically occurring during exposure to cold and seen in the cold-treated control rats. Thus, increased weight of the heart, kidneys, adrenals and brown adipose tissue, increased dipsogenic responsiveness to angiotensin II, increased urinary outputs of norepinephrine and epinephrine, and increased food and water consumption were observed in all rats, treated and untreated, during exposure to cold. Similarly, daily injection of clonidine attenuated the elevation of blood pressure but also failed to prevent the other adaptive physiological changes characteristic of cold. These results are consistent with the hypothesis that the RAA system plays a role in the development of the cold-induced elevation of blood pressure.

Effect of Chronic Dietary Treatment with Z-Tryptophan on the Development of Cold-Induced Hypertension in Rats

This study was designed to assess the effect of chronic dietary administration (2.5 and 5.0% by weight) of the neutral amino acid, L-tryptophan, on the development of hypertension during chronic exposure to cold. In addition, a warm-adapted and cold-treated control group receiving unsupplemented food were used. Chronic administration of the lower dose of L-tryptophan (850 mg/day) prevented the elevation of blood pressure attenuated cardiac hypertrophy, and had no effect on body weight during exposure to cold. The higher dose of L-tryptophan (1,690 mg/day) attenuated the rate of blood pressure increase, did not affect cardiac hypertrophy, attenuated the gain in body weight, and increased the urinary output of epinephrine. Thus, this dose may be associated with some toxicity. Both doses of tryptophan failed to prevent certain other responses characteristically occurring during exposure to cold: i.e. increased weight of the kidneys, adrenal glands and brown adipose tissue; increased food and water consumption; increased dipsogenic responsiveness to angiotensin II, and increased plasma aldosterone concentration. The results indicate that chronic dietary administration of L-tryptophan (850 mg/day) can prevent the development of cold-induced hypertension, as it can in all other models of hypertension tested thus far in rats.

Non-Invasive Assessment of the Cardiovascular Eicosanoids, Thromboxane A2 and Prostacyclin, in Randomly Sampled Males, with Special Reference to the Influence of Inheritance and Environmental Factors

1. We studied, in a random sample of 385 nonsmoking men born in 1968-1969 and 31 men born in 1913 or 1923, whether inheritance and environmental factors influenced platelet activity and vessel wall prostacyclin formation, as reflected non-invasively by the urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 (2,3-dinor-thromboxane B2, Tx-M) and prostacyclin (2,3-dinor-6-keto-prostaglandin F1 alpha, PGI-M), respectively. 2. Fathers of young men with high platelet activity did not excrete more Tx-M than fathers of young men with low platelet activity. Men born in 1913 or 1923 displayed higher Tx-M (563 versus 128 pg/mg of creatinine, P less than 0.001) and PGI-M (163 versus 130 pg/mg of creatinine, P less than 0.01) excretion than those born in 1968-1969. Excretion of both Tx-M and PGI-M was correlated to the urinary output of noradrenaline and adrenaline. 3. Well-trained subjects did not differ in their excretion of Tx-M or PGI-M from those who did not exercise regularly. A recent acute infection was also unrelated to the excretion of Tx-M or PGI-M. PGI-M excretion was, however, significantly correlated to Tx-M excretion (r = 0.51, P less than 0.001). 4. This study provides the first non-invasive evidence that advancing age and sympathoadrenal tone are positively correlated to platelet activity in randomly sampled men, and that paternal inheritance, physical fitness and recent infection lack correlation to platelet activity.

Differential control of glycogenolysis and flow by arterial and portal acetylcholine in perfused rat liver

The effects of acetylcholine on glucose and lactate balance and on perfusion flow were studied in isolated rat livers perfused simultaneously via the hepatic artery (100 mmHg, 25-35% of flow) and the portal vein (10 mmHg, 75-65% of flow) with a Krebs-Henseleit bicarbonate buffer containing 5 mM-glucose, 2 mM-lactate and 0.2 mM-pyruvate. Arterial acetylcholine (10 microM sinusoidal concentration) caused an increase in glucose and lactate output and a slight decrease in arterial and portal flow. These effects were accompanied by an output of noradrenaline and adrenaline into the hepatic vein. Portal acetylcholine elicited only minor increases in glucose and lactate output, a slight decrease in portal flow and a small increase in arterial flow, and no noradrenaline and adrenaline release. The metabolic and haemodynamic effects of arterial acetylcholine and the output of noradrenaline and adrenaline were strongly inhibited by the muscarinic antagonist atropine (10 microM). The acetylcholine-dependent alterations of metabolism and the output of noradrenaline were not influenced by the alpha 1-blocker prazosin (5 microM), whereas the output of adrenaline was increased. The acetylcholine-dependent metabolic alterations were not inhibited by the beta 2-antagonist butoxamine (10 microM), although the overflow of noradrenaline was nearly completely blocked and the output of adrenaline was slightly decreased. These results allow the conclusion that arterial, but not portal, acetylcholine caused sympathomimetic metabolic effects, without noradrenaline or adrenaline being involved in signal transduction.

Copper-Deficient Mice Have Higher Cardiac Norepinephrine Turnover

Norepinephrine metabolism was investigated in 6-wk-old male Swiss albino copper-deficient and copper-supplemented mice. Beginning 4 d after birth of pups, dams were fed a diet low in copper (Cu) (0.4 mg/kg) and offspring were weaned to this diet at 21 d of age. Half the dams and their respective offspring received Cu (20 micrograms/ml) in the drinking water (+Cu) and served as controls. Unsupplemented offspring (-Cu) had lower liver Cu levels, exhibited anemia, and had increased heart weights but normal body weights compared to +Cu mice. Urinary output of norepinephrine and dopamine was higher, whereas output of creatinine and epinephrine was not different in -Cu mice compared to +Cu mice. Both fractional and calculated turnover of norepinephrine following inhibition of tyrosine 3-monooxygenase by alpha-methyl-p-DL-tyrosine methyl ester (alpha-MT) was higher in hearts from -Cu mice than in those from +Cu mice. Hearts and spleens from -Cu mice appeared to have higher tyrosine 3-monooxygenase activity as judged by increasing rates of L-dihydroxyphenylalanine accumulation following injection of m-hydroxybenzylhydrazine (NSD-1015), an inhibitor of aromatic amino acid decarboxylase. Turnover rates of norepinephrine for cerebellum were not different between +Cu and -Cu mice. Loss of norepinephrine from adrenal glands of mice injected with alpha-MT was not observed in the 8-h period studied. The smaller norepinephrine pool observed in organs of -Cu mice may have resulted from lower synthesis due to limiting dopamine-beta-monooxygenase activity and to higher turnover.

Adrenal responses to splanchnic nerve stimulation in conscious calves given naloxone.

1. The effects of stimulating the peripheral end of the right splanchnic nerve in the presence of naloxone (2 mg kg-1) have been investigated in conscious 3 to 6-week-old calves. 2. Mean aortic blood pressure rose to significantly higher levels during splanchnic stimulation in bursts at 40 Hz for 1 s at 10 s intervals than it did during stimulation at the corresponding continuous frequency (4 Hz). Furthermore, naloxone significantly reduced the fall in mean vascular resistance in response to both patterns of stimulation. 3. The output of catecholamines from the adrenal gland, together with the proportion of noradrenaline released, was significantly enhanced by stimulating the splanchnic nerves in bursts in animals pre-treated with naloxone and the proportion of noradrenaline released also increased. In both cases the output of adrenaline and noradrenaline was within the same range as that reported previously in normal control animals. 4. Naloxone significantly increased the amounts of enkephalin-like immunoreactivity and corticotrophin-releasing factor (CRF)-like immunoreactivity released from the adrenal gland in response to splanchnic nerve stimulation and raised the proportion of total to free met5-enkephalin that was secreted. 5. Naloxone also inhibited the rise in plasma adrenocorticotrophic hormone (ACTH) concentration during continuous stimulation at 4 Hz, but not during stimulation at 40 Hz in bursts. Under these latter conditions the output of cortisol apparently directly from the adrenal gland was inhibited. The finding that splanchnic nerve stimulation can potentiate the output of cortisol in response to ACTH was confirmed. 6. These results provide evidence that release of enkephalins and of CRF from the adrenal is inhibited by activating opioid receptors within the gland itself.

Aggressiveness and hyperactive behaviour as related to adrenaline excretion

The central question concerns the relationship between aspects of behaviour and physiological reactions. Measures of sympathetic‐adrenal activity in terms of adrenaline excretion in a normal and a stressful situation as well as teacher ratings of behaviour were analysed for a representative group of 86 boys aged 13. Adrenaline excretion was in both situations significantly negatively related to ratings of aggressiveness, motor restlessness, and concentration difficulties and also to the sum of the latter two, used as an indicator of hyperactive behaviour. The association between hyperactive behaviour and adrenaline excretion persisted in the stressful situation when aggressiveness was controlled, whereas there was no significant relationship between aggressiveness and adrenaline output when hyperactive behaviour was controlled. Furthermore, hyperactive boys differed significantly from non‐hyperactive boys in displaying lower adrenaline excretion in both situations. The results are discussed in terms of low sympathetic‐adrenal reactivity to external demands as a risk factor and as a possible indicator of vulnerability for social and/or pervasive conduct disturbances.