Increase In Plasma Corticosteroids Research Articles

Interaction of acute hypoxia and body temperature on metabolic and endocrine responses in the neonatal rat: effect of preventing spontaneous hypothermia

Neonatal hypoxia is a serious condition that leads to spontaneous hypothermia and an increase in plasma corticosteroids. We hypothesized that maintenance of isothermia during acute hypoxia augments the adrenocortical and metabolic stress response. Hypoxia (8% O2) was induced for 3 h in postnatal day (PD) 2 and PD8 rats; either spontaneous severe hypothermia was allowed or isothermia was maintained with external heat. Hypothermic hypoxia caused an increase in plasma corticosterone in PD2 and PD8 pups; this response was augmented by isothermia. In PD2 rats, the corticosterone response was ACTH-independent. In PD8 rats, plasma ACTH increased in response to hypoxia and was augmented with isothermia. Plasma glucose was not changed in PD2 rats; in PD8 rats, hypothermic hypoxia induced an increase in plasma glucose and insulin, whereas isothermic hypoxia induced a decrease in plasma glucose and insulin. Adrenal and metabolic responses to hypoxia change with neonatal age and body temperature. Maintenance of isothermia augments the adrenocortical response to hypoxia and leads to low blood glucose in PD8 rats. It may be prudent to allow hypothermia during episodes of acute hypoxia in the neonate.

Neuroendocrine regulation of pituitary-adrenal function during fetal life.

During late gestation there is a rise in the concentration of corticosteroids in the fetal circulation that is essential for the coordinated maturation of many fetal organ systems and is a key component in the endocrine pathway leading to the onset of birth. Fetal plasma concentrations of adrenocorticotrophin (ACTH) increase during late gestation and this rise precedes the increase in plasma corticosteroids. Paradoxically, ACTH and cortisol concentrations increase concomitantly even though cortisol would normally be expected to exert negative feedback effects to inhibit pituitary ACTH secretion. Elucidating the neuroendocrine signals that cause the increase in fetal ACTH, despite the elevated concentrations of cortisol at this time, will therefore provide vital clues as to the trigger for fetal organ maturation and birth. This article describes the normal ontogeny of the hypothalamo-pituitary-adrenal axis, discusses the neuroendocrine signals that trigger the increase in fetal ACTH secretion and provides potential explanations for the concomitant rise in ACTH and cortisol.

Protein sparing in skeletal muscle during prolonged starvation. Dependence on lipid fuel availability.

Previous studies indicated that protein sparing in skeletal muscle during prolonged starvation depends on the availability of lipid fuels. To test this relationship further, fasted rats conserving protein were treated in vivo for 6-8 h with the antilipolytic agent nicotinic acid (NA) or with tetradecylglycidate (TDGD), an inhibitor of long-chain fatty acid oxidation. After treatment, protein synthesis and degradation in skeletal muscle were evaluated with the perfused rat hindquarter. NA treatment decreased plasma 3-hydroxybutyrate and free fatty acids and increased plasma urea and urine urea excretion, indicating increased breakdown of body protein. TDGD produced similar metabolic effects, except that plasma free fatty acids were markedly increased as a result of inhibition of fatty acid oxidation. NA and TDGD also decreased plasma insulin and increased plasma corticosteroid. Inhibition of lipid metabolism in vivo resulted in accelerated loss of protein from skeletal muscle due to decreased protein synthesis and increased protein breakdown. NA increased both total (i.e., tyrosine release) and myofibrillar (i.e., 3-methylhistidine release) protein breakdown, whereas TDGD increased the breakdown of only nonmyofibrillar proteins (i.e., 3-methylhistidine release by perfused hindquarter was not altered). These data indicate that lipid fuels may directly modulate protein metabolism in muscle during prolonged starvation and may prevent a rise in catabolic hormones. They also indicate that free fatty acids may directly attenuate the breakdown of myofibrillar proteins in muscle during prolonged starvation and that this may be unrelated to their oxidation.

Characteristics of the receptors which mediate the stimulation of ACTH secretion by vasopressin in conscious dogs.

In order to characterize the receptors which mediate the adrenocorticotropic hormone (ACTH) response to vasopressin in conscious animals, plasma 11-hydroxycorticosteroid concentration was measured in conscious dogs during the infusion of vasopressin or structural analogs of vasopressin which exhibit selective antidiuretic or vasoconstrictor activity. Vasopressin (1.0 ng/kg/min for 60 min) increased mean arterial pressure, decreased heart rate and increased plasma corticosteroid concentration from 1.0 +/- 0.2 to 2.2 +/- 0.2 micrograms/dl (p less than 0.001). A specific antagonist of the vasoconstrictor activity of vasopressin, d(CH2)5MeTyrAVP (10 micrograms/kg), completely blocked the cardiovascular and corticosteroid responses to vasopressin. A selective vasoconstrictor (V1) agonist, PheOrnOT (1.0 ng/kg/min), which produced the same cardiovascular responses as vasopressin, increased plasma corticosteroid concentration from 1.1 +/- 0.1 to 2.9 +/- 0.9 micrograms/dl (p less than 0.005). In marked contrast, a selective antidiuretic (V2) agonist, dDAVP (1.0 ng/kg/min) had no effect on blood pressure, heart rate or plasma corticosteroid concentration. These results indicate that the stimulation of ACTH release by vasopressin in conscious dogs is mediated by receptors which resemble vasoconstrictor-type (V1) receptors rather than antidiuretic-type (V2) receptors.

Feedback inhibition of adrenocorticotropin and vasopressin responses to hypoxia by physiological increases in endogenous plasma corticosteroids in dogs.

We examined the influence of increases in plasma corticosteroids produced by ACTH infusion on subsequent ACTH and vasopressin (AVP) responses to hypoxia in anesthetized dogs. Basal and stimulated ACTH levels were inhibited by increases in corticosteroids. Moderate increases in corticosteroids (5.2 micrograms/dl) caused a 50% reduction in the subsequent integrated ACTH response to hypoxia. Maximal increases in corticosteroids eliminated the integrated ACTH response to hypoxia. In addition, AVP responses to hypoxia were attenuated by prior maximal elevations in corticosteroids. Physiological elevation of corticosteroids inhibits subsequent ACTH and AVP responses to hypoxia.

Immunoreactive corticotropin-releasing factor concentrations in cerebrospinal fluid from patients with hypothalamic-pituitary-adrenal disorders.

The concentrations of immunoreactive corticotropin-releasing factor (I-CRF) in human cerebrospinal fluid (CSF) were measured utilizing immunoaffinity chromatography and RIA in patients with no endocrine disease, patients with Cushing's disease, Nelson's syndrome, Sheehan's syndrome, Addison's disease and steroid treated patients. On high performance liquid chromatography, the elution profile and retention time of I-CRF in CSF were not identical with ovine CRF. I-CRF concentrations in CSF from patients with Cushing's disease and Sheehan's syndrome were lower than those from normal subjects, however those from patients with Nelson's syndrome and Addison's disease were within the normal range. I-CRF concentrations in CSF from patients with Cushing's disease returned to normal levels 2-9 months after pituitary adenomectomy. These results suggest that CSF I-CRF concentrations are reduced by increased plasma corticosteroid levels.

Stress Response and Blood Characteristics of Channel Catfish (Ictalurus punctatus) after Anesthesia with Etomidate

Continuous anesthesia of channel catfish (Ictalurus punctatus) with 0.6 mg/L etomidate for 96 h caused a small but statistically significant decrease in plasma protein concentration at all sampling periods. Hemoconcentration, indicated by increased total erythrocyte count, hematocrit, and hemoglobin, resulted from anesthesia with 1–4 mg/L etomidate for 30–180 min. Periodic removal of fish from 400-L troughs stressed other unanesthetized fish in the trough causing significantly increased plasma corticosteroid, glucose, and protein concentrations. Anesthetized fish were not stressed by the periodic sampling. Fish anesthetized with 3 mg/L etomidate and then confined in a net for 10 min had reduced plasma Cortisol response and no significant plasma glucose increase compared with unanesthetized controls. Anesthesia did not prevent hyperchloremia that developed 3 h after the 10-min confinement. No histological changes were found in fish anesthetized with etomidate. Anesthesia with etomidate before netting could be useful when handling fish because of the reduced stress response.

Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine

Adinazolam, which is a 1-dimethylaminomethyl triazolobenzodiazepine, is an effective anxiolytic agent as defined by suppression of stress-induced increases in plasma corticosteroids. Adinazolam is also an effective antagonist of pentylenetetrazole. The 1-dimethylaminoethyl triazolo analog, U-43,465F, was inactive in the stressed rat test and only weakly active against pentylenetetrazole. Adinazolam and U-43,465F have been previously shown to have antidepressant activity in classical screening tests. They have also been found to potentiate the effect of norepinephrine and this is consistent with the activity of the known antidepressants; U-43,465F was found to be equieffective to imipramine in this test. Adinazolam was also effective; however, the magnitude of the potentiation was not as great. The uptake of norepinephrine was only weakly affected by either compound. Potentiation or uptake of serotonin were not significantly-altered pharmacological factors. Receptor binding studies were negative except at the benzodiazepine receptor. Chronic treatment with adinazolam did not decrease the number of beta-adrenergic receptors in the cerebral cortex of the rat, in contrast to the positive effect of imipramine. The discovery of triazolobenzodiazepines with antidepressant activity is of special interest. These agents will hopefully have lower toxicity than the tricyclic antidepressants and thus possess a more favourable therapeutic index. This would be advantageous in the treatment of depression.

Influence of the pituitary-adrenal axis on the induced release of luteinizing hormone in rams

Treatment of intact rams with ACTH increased plasma corticosteroids and significantly reduced the ability of LH releasing hormone (LHRH) to elicit the release of LH. Infusion of cortisol at a rate which increased plasma corticosteroid concentrations to above that observed after injection of ACTH did not affect the ability of LHRH to induce the release of LH. In adrenalectomized rams LH release in response to LHRH was inhibited during ACTH treatment but was not affected in the absence of ACTH. Therefore, ACTH reduced the responsiveness of the anterior pituitary gland to LHRH through a mechanism not involving the adrenal gland.

Inhibition of the adrenocorticotropin and corticosteroid responses to hypoglycemia after prior stress.

We have tested the efficacy of prior stress-induced increases in corticosteroids on inhibition of the ACTH response to hypoglycemia induced 2 h later. Five dogs were studied in each of five experiments. In each experiment, there were two stimulus periods; in the first, 5% dextrose, 3 or 10 micrograms/kg X min nitroprusside, or 0.05 or 0.10 U/kg insulin was administered, and in the second, 0.10 U/kg insulin was administered. Whereas prior infusion of 5% dextrose did not affect the subsequent ACTH response to 0.10 U/kg insulin, prior stimulation of the pituitary-adrenal axis had a significant effect on the subsequent ACTH response to 0.10 U/kg insulin. The integrated ACTH response to hypoglycemia was significantly reduced by prior stimulation by either 10 micrograms/kg/min nitroprusside or 0.10 U/kg insulin, although the intensity of the hypoglycemia during the second stimulus period was not altered by any of the prior stimuli. Overall, the magnitude of the suppression of the pituitary-adrenal response to hypoglycemia was significantly related to the increase in plasma corticosteroids produced by the first stimulus, and was consistent with the degree of corticosteroid feedback inhibition of ACTH observed in previous studies after ACTH or corticosteroid infusion. Therefore, we conclude that prior stimulation of the hypothalamo-pituitary-adrenal axis of conscious dogs by hypotension or hypoglycemia inhibits subsequent responses in proportion to the corticosteroid feedback signal produced.

Feedback inhibition of adrenocorticotropic hormone by physiological increases in plasma corticosteroids in conscious dogs.

We have tested the effect of physiological increases in plasma corticosteroids in conscious dogs on the levels of basal and hypoglycemia-stimulated adrenocorticotropic hormone (ACTH) 2 h later. Increases in plasma corticosteroids, produced by infusion of alpha-1-24 ACTH or corticosteroids for 40 min, suppressed basal and stimulated ACTH levels. The magnitude of inhibition produced by an increase in plasma corticosteroids induced by the infusion of ACTH was equivalent to the inhibition produced by the same increase in plasma corticosteroids induced by corticosteroid infusion. The infusions did not affect basal plasma glucose concentrations or the decrease in plasma glucose concentrations after administration of 0.1 U insulin/kg. Basal ACTH concentration was less sensitive than hypoglycemia-stimulated ACTH concentration to corticosteroid-induced suppression. Basal and stimulated secretion were significantly inhibited in all dogs after approximately half-maximal increases in plasma corticosteroids; maximum inhibition occurred after maximal increases in plasma corticosteroids. Therefore, physiological increments in plasma corticosteroids, similar to those produced by acute stress, are effective suppressors of subsequent stress-induced ACTH secretion.

Plasma Corticosteroids and Chlorides in Striped Bass Exposed to Tricaine Methanesulfonate, Quinaldine, Etomidate, and Salt

Abstract Plasma chloride and corticosteroid concentrations were measured in yearling striped bass (Morone saxatilis) exposed to 25 mg/L tricaine methanesulfonate, 2.5 mg/L quinaldine, or 0.1 mg/L etomidate (an experimental drug), alone and in combination with 10 g/L salt (NaCl). Plasma chloride levels were unaffected in all treatments during a 15-min exposure and during a 10-min period of close confinement in a dipnet. Plasma corticosteroids increased in fish exposed to salt alone and in fish exposed to tricaine methanesulfonate or quinaldine, either alone or in combination with salt. Etomidate alone or combined with salt limited the increase in plasma corticosteroids during exposure and confinement. Etomidate appears to be a useful drug for suppressing physiological changes during the handling and transportation of striped bass.

Adrenal sensitivity to adrenocorticotropin in normovolemic and hypovolemic conscious dogs.

In the preceding paper we reported that conscious dogs respond to 15 ml/kg hemorrhage with increases in plasma corticosteroids that are often unaccompanied by measured increases in plasma ACTH. These experiments were designed to test for a hemorrhage-induced shift in adrenal sensitivity to ACTH. Hemorrhage-induced changes in adrenal sensitivity were tested in two ways. First, dexamethasone-pretreated dogs were subjected to four 5-min steps of ACTH infusion, increasing in rate from 38 to 380 ng/min. The increasing rates of ACTH infusion elevated plasma ACTH to levels that were linearly related to the ACTH infusion rate, and elevated plasma corticosteroids to levels that were linearly related to the logarithm of the ACTH infusion rate and the plasma ACTH concentration. The magnitude of the peripheral plasma corticosteroid response to the ACTH step infusion was not changed either by simultaneous hemorrhage or by step infusion or hemorrhage 1.5–2 h earlier. Second, dexamethasone-pretreated dogs were subjected...

EFFECT OF VASOPRESSIN BLOCKADE ON BLOOD PRESSURE REGULATION DURING HEMORRHAGE IN CONSCIOUS DOGS

The role of vasopressin in the regulation of blood pressure during nonhypotensive hemorrhage was assessed in conscious dogs. An antagonist of the vasoconstrictor activity of vasopressin was administered (10 microgram/kg) to four normal dogs five min prior to the commencement of a 15 min arterial hemorrhage (1 ml/kg/min). The withdrawn blood was reinfused 15 min after completion of the hemorrhage. In the absence of vasopressin blockade, blood pressure and heart rate did not change significantly, while plasma renin activity increased from 3.8 +/- 0.9 to 10.8 +/- 3.1 ng/ml/3h (P less than 0.005), and plasma corticosteroid concentration increased from 1.5 +/- 0.8 to 8.6 +/- 2.0 microgram/dl (P less than 0.001). Following vasopressin blockade, the same hemorrhage decreased mean arterial pressure from 96 +/- 264 +/- 7 mmHg (P less than 0.001), increased heart rate from 71 +/- 10 to 130 +/- 23 beats/min (P less than 0.05), increased plasma renin activity from 7.1 +/- 0.8 to 30.3 +/- 6.7 ng/ml/3h (P less than 0.005) and increased plasma corticosteroid concentration from 1.9 +/- 0.7 to 11.4 +/- 1.2 microgram/dl (P less than 0.001). These data indicate that vasopressin plays an important role in blood pressure regulation during mild hemorrhage in conscious dogs.

Effect of behavioral stress on plasma levels of growth hormone in sheep

In this study the effects of both acute and prolonged behavioral stress on the secretion of growth hormone was determined. Restraint of lambs in the dark chamber for ten minutes resulted in a significant increase in plasma corticosteroids without having any influence on the secretion of growth hormone. When the lambs were exposed to ten days of two-way active avoidance conditioning, there was a marked increase in plasma corticosteroids following the conditioning sessions; however, again the secretion of growth hormone was not affected. It was concluded from these data that behavioral stress does not appear to influence the secretion of growth hormone in sheep.

Corticotropin- and lysine-vasopressin induced changes of plasma corticosteroids and testosterone in the adult male pig

Intravenous injection of 10.0 micrograms/kg body weight synthetic corticotropin (1-24 ACTH) into chronically cannulated boars resulted in significantly elevated plasma corticosteroid and testosterone levels between 20 and 140 min (corticosteroids) and 20--80 min (testosterone) after injection. Administration of lysine-vasopressin (LVP) at doses of 0.1, 0.2 and 0.4 IU/kg body weight elicited a significant increase of plasma corticosteroids between 20 and 40 min after injection; on the other hand, plasma testosterone concentrations tended to fall when compared to pre-treatment levels. From our results it can be concluded that exogenously applied ACTH can effectively stimulate the release of corticosteroids and testosterone. Intravenous administration of LVP results in significantly, although not maximally increased plasma corticosteroid concentrations; the release of endogenous ACTH induced by LVP injection, on the other hand, appeared to be too small to stimulate testosterone release significantly.

New method of obtaining cinchophen ulcer in dogs.

Cinchophen injected into the cerebral ventricle reacted with the hypothalamus somewhere in the vicinity ventricle, and produced a release of ACTH as indicated by a rise in peripheral plasma 11-OHCS concentration in the dog. The amount of cinchophen injected into the ventricle corresponds to about 1/600 of the dose required to produce the same effect by the intravenous route. Repeated intraventricular injections of cinchophen were effective in producing gastric erosions and ulcers at smaller doses than the intravenous one (1/100 and 1/400). Damage to the gastric wall might be due to a mechanism involving a localized portion of the hypothalamus and/or via a cerebral ventricle. Bilateral truncal vagotomy did not have any effect on chronic ulcer production. The cinchophen ulcerations were accompanied by an increase in plasma corticosteroids. The new experimental technique for producing peptic ulcer in dogs via a central neurohumoral mechanism is described.

Effect of angiotensin II and glucocorticoids on plasma angiotensinogen concentration in the dog.

The increase in plasma angiotensinogen concentration produced by angiotensin II infusion in the dog is accompanied by an increase in plasma corticosteroid concentration and is prevented by adrenalectomy. The present study was undertaken to test the possibility that the angiotensinogen response to angiotensin is mediated via an increase in glucocorticoid secretion. Infusion of angiotensin II (3-6 mug/h for 5 h) into the third cerebral ventricle of five dogs increased plasma corticosteroid concentration from 3.5+/-0.6 to 11.8+/-1.5 mug/dl (P less than 0.025) but did not increase plasma corticosteroid concentration from 2.7+/-0.4 to 7.8+/-1.5 mug/dl (P less than 0.05) but again failed to increase plasma angiotensinogen concentration. On the other hand, more prolonged glucocorticoid treatment with dexamethasone produced a significant increase in plasma angiotensinogen concentration within 24 h. Intravenous infusion of angiotensin II (50 mug/h for 5 h) in five acutely hypophysectomized dogs receiving a cortisol infusion caused only a small increase in plasma corticosteroid concentration (5.0+/-0.5 TO 6.9+/-0.6 mug/dl, P less than 0.02) but increased plasma angiotensinogen concentration from 967+/-122 to 1,358+/-204 ng/ml (P less than 0.02). These results indicate that although glucocorticoids can increase plasma angiotensinogen concentration, the angiotensinogen response to angiotensin II is not dependent on increased glucocorticoid secretion.

Plasma corticosteroid, circulating leukocyte and milk somatic cell responses to Escherichia coli endotoxin-induced mastitis.

SummaryA mammary quarter in each of 4 cows was infused with 0.5 mg E. coli endotoxin to determine its effect on plasma corticosteroids, circulating leukocytes and milk somatic cells. At 1.5 hr following endotoxin infusion, segmented neutrophils decreased 23%, and by 5 hr dropped 93%. A shift left in the differential circulating leukocyte count began at 2.5 hr and reached maximum proportions between 18-24 hr postendotoxin infusion. Circulating lymphocytes, monocytes and eosinophils were all depressed in response to endotoxin. Plasma corticosteroid concentrations increased (P < 0.01) 2 hr following endotoxin infusion, reached maximum concentrations at 4 hr, then returned to prein-fusion concentrations by 12 hr. The initial decrease in circulating lymphocytes at 2.5 hr was not attributed to the lytic effect of the plasma corticosteroids, since depressions in circulating lymphocytes occurred too soon (0.5 hr) after the increase in plasma corticosteroids. The high plasma corticosteroid concentration appeared t...

The effect of minor tranquilizers on stress-induced increases in rat plasma corticosteroids.

In this study a variety of psychoactive drugs were evaluated for their ability to block a stress-induced elevation in rat plasma corticosteroids. Stress was applied by placing the rats in different cages and moving them to a novel environment which resulted in a rapid increase in plasma corticosteroids, near maximal with 30 min, followed by a decrease to normal by 2 h. Meprobamate, phenobarbital, diazepam and several other benzodiazepines, all of which exhibit anxiolytic properties, were able to block the stress-induced increase. U-33,030 and U-31,889, two triazolobenzodiazepine derivatives, were the most potent compounds tested. No other type of psychoactive compound demonstrated this activity.