Biomedical subjects

M F Dallman

Publications and source records attributed to M F Dallman.

At least 91 records · Page 5Linked to original sources

PubMed1991

Drug effects on orthostatic intolerance induced by bedrest.

Effective and practical preventive procedures for postflight orthostatic intolerance are highly desirable. The current practice of attempts to expand plasma volume by ingestion of salt and fluids before reentry has proven benefits. This study evaluated alternative options using fludrocortisone (F) to expand plasma volume (PV), dextroamphetamine (Dex) to enhance norepinephrine (NE) release and atropine (A) to reduce the effects of vagal stimulation. Seven subjects with proven post-bedrest orthostatic intolerance returned for a 7-day 6 degrees head-down bedrest study. F (0.2 mg) was given at 8:00 AM and 8:00 PM the day before and 8:00 AM the day the subjects got out of bed (2 hours before standing). PV was measured before and 1 hour after the last dose of F. D (5 mg) and A (0.8 mg) were then taken orally 1 hour before the stand test. F expanded PV by 16% and caused sodium retention. Four of the 7 subjects stood for 1 hour post-bedrest and HR, plasma NE and PRA responses to standing were greatly enhanced and sustained. Although there was a narrowing of pulse pressure, the ability to overcome orthostatic intolerance with these countermeasures was largely due to vasoconstriction and sustained high heart rate. The existing literature on pharmacologic countermeasures for post-flight and post-bedrest orthostatic hypotension is reviewed, and the results are discussed in that context.

Adult↗

PubMed1991

Regulation of basal ACTH secretion by corticosterone is mediated by both type I (MR) and type II (GR) receptors in rat brain.

The mechanisms involved in the physiology of the secretion of ACTH are reviewed. The secretion is regulated by the biological consequences of the occupancy of high affinity mineralocorticoid (MR) and lower affinity glucocorticoid receptors (GR) for corticosterone at specific sites of the rat brain. The regulation by this mechanism of basal secretion during the circadian rhythm, the effect of adrenalectomy and of corticosterone replacement is discussed. Experiments with RU486, a specific glucocorticoid antagonist, suggest that occupancy of both MR and GR is required for normal control of ACTH at the time of peak activity. The occupancy of the GR for a few hours per day apparently suffices to maintain steady levels of the products of GR-responsive genes throughout the body.

Adrenal Glands↗

PubMed1991

Stress-induced adrenocorticotropin secretion: diurnal responses and decreases during stress in the evening are not dependent on corticosterone.

To test whether the diurnal rhythm in stress responsiveness is dependent on corticosterone (B)-mediated negative feedback, the responses of intact (SHAM) and adrenalectomized (ADX) rats to restraint for 3-90 minutes or ip injection with saline in the morning (AM) and the evening (PM) were compared. In both SHAM and ADX rats, ACTH responses to restraint stress were larger in the AM. In intact rats, this could have resulted from both fast negative feedback, due to the rate of rise of B during the stress in the PM, and delayed negative feedback, due to the high basal concentrations of B before the stress in the PM. However, this diurnal pattern of stress responsiveness was not dependent on B, as the same relative responses to restraint and ip injection were found in ADX rats. To determine whether the lack of response of ADX rats in the PM to stress was due to a loss of sensitivity to endogenous secretagogues, ADX rats were given CRF + arginine vasopressin (AVP) while anesthetized with ether after 30 min of restraint. In both the AM and the PM, the pituitaries were able to respond to exogenous secretagogues. A second novel finding was that in the PM, but not the AM, plasma ACTH concentrations in the ADX rats decreased substantially during the period of restraint, despite the lack of B-mediated negative feedback. In the AM and the PM, ADX rats were restrained for 30 min and then stressed with ether for 6 min. The ACTH concentrations were not different before and after ether, suggesting that, although the pituitaries of ADX rats are able to respond to exogenous CRF + AVP after stress, an additional stress of ether exposure no longer stimulates endogenous CRF and AVP release after 30 min of restraint at either time of day. After 90 min of restraint in the AM and the PM, the relationship between ACTH and B was positive, not negative, providing no evidence of ongoing B-mediated negative feedback in the SHAM rats. Therefore, the same mechanism responsible for the decrease in ACTH secretion in ADX rats may occur in SHAM rats as well. From these results, we conclude that the diurnal rhythm in stress responsiveness and, in the PM in the ADX rats, the decrease in plasma ACTH during stress, are largely independent of B.

Adrenalectomy↗

PubMed1991

The pituitary-adrenocortical system of neonatal rats is responsive to stress throughout development in a time-dependent and stressor-specific fashion.

The responsiveness of the neonatal hypothalamus-pituitary-adrenal (HPA) axis to stress has been thought to be impaired or diminished during the first 2 weeks of life. Although we previously found full responsiveness of the hypothalamus-pituitary unit to adrenalectomy in young rats [days (d) 5-10], we failed to measure a significant increase in ACTH 10 min after ether administration until d14 of age. These studies were, therefore, designed to test the functional activation of the HPA axis after a single or repeated exposures to stress. Both qualitative (time-course, stressor-specific, circadian) and quantitative changes in the ACTH and corticosterone (B) responses to various stressors were tested during the first 10 days of life. Exposure to 3 min of ether vapor increased ACTH and B secretion (P less than 0.05-0.01) in 1-, 5-, and 10-d-old rats, with an increasing amplitude of both ACTH and B responses as a function of age. Peak secretion of ACTH occurred 5 min after the onset of stress (122 +/- 3.8 to 359 +/- 54 pg/ml on d1-10), while the time of maximal B increased as a function of age. Other stressors, such as maternal separation (12 h), cold (4 C; 60 min), or histamine injection (4 mg/kg BW, ip), provoked significant and stressor-specific ACTH and B responses in 10-d old rats. Histamine administration increased ACTH secretion above that of vehicle-injected rats, with a peak of secretion 15 min after drug injection (272 +/- 29 vs. 127 +/- 8 pg/ml; P less than 0.01). Histamine-induced B secretion peaked at 60 min (3.7 +/- 0.5 micrograms/dl). In contrast to early responses observed after ether, separation, or histamine stress, cold stress in 10-d-old pups caused a large ACTH and B release 4 h after the onset of cold compared to that in maternally deprived pups [ACTH: cold, 457 +/- 61 pg/ml; separated, 150 +/- 14 (P less than 0.01); B: cold, 3.3 +/- 0.4 micrograms/dl; separated, 1.8 +/- 0.2 (P less than 0.05)]. We did not detect morning-evening (AM-PM) differences in either the pattern or the magnitude of the ACTH or B response to maternal separation or cold stress. Suppression of cold-induced ACTH release by B injection (1 mg/kg BW) 2 h before stress was observed until 4 h after stress in the AM and PM, whereas when given after cold, B was less effective in the PM than in the AM at preventing the rise in ACTH levels observed at 4 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗

PubMed1991

Chronic streptozotocin diabetes in rats facilitates the acute stress response without altering pituitary or adrenal responsiveness to secretagogues.

We have used streptozotocin (STZ)-induced diabetes in rats to determine whether this represents a sustained stimulus to the adrenocortical system and whether STZ-diabetic rats are able to mount an acute stress response. Furthermore, we compared pituitary responsiveness to CRF and/or arginine vasopressin, and adrenal responsiveness to ACTH in STZ- vs. vehicle-treated rats. We also compared the efficacy of dexamethasone inhibitory feedback in STZ-diabetic and control rats. Our results show that STZ-treated rats chronically hypersecrete corticosterone (B) as evidenced by their decreased thymus weights, their increased urinary B excretion, and their elevated mean plasma B levels during the light hours of the day. Despite the evidence for sustained hypersecretion of B, STZ-treated rats showed greater and more prolonged ACTH and B responses to the acute stress of histamine injection. However, when tested separately, neither pituitary nor adrenal responsiveness to their secretagogues were increased in STZ-diabetic compared to control rats. Dexamethasone inhibition of stress-induced B secretion was tested using two different paradigms: pentobarbital-anesthetized rats were given iv injections of acid saline, and awake rats were given ip injections of histamine. In both experiments the STZ-treated rats were relatively resistant to glucocorticoid inhibition of stress responses. This finding, taken together with the exaggerated ACTH and B responses to stress, strongly suggests that the facilitatory effects of chronic STZ-diabetes are a consequence of changes in sensitivity of central neural components of the adrenocortical system to stimulatory and/or inhibitory inputs, in conjunction with changes in glucocorticoid feedback sensitivity.

Adrenal Glands↗

PubMed1990

Rat insulin-like growth factor-I and -II mRNAs are unchanged during compensatory adrenal growth but decrease during ACTH-induced adrenal growth.

The insulin-like growth factors (IGFs) may be important autocrine and paracrine mediators of organ growth. We used solution-hybridization/ribonuclease protection assays to examine IGF-I and IGF-II mRNA abundance during hypertrophy or the rat adrenal gland induced by unilateral adrenalectomy or by adrenocorticotropic hormone (ACTH) infusion. Adrenal IGF-I mRNA did not change during the period of rapid organ growth at 18 or 66 h after unilateral adrenalectomy. ACTH infusion induced a time- and dose-dependent decrease in adrenal IGF-I mRNA despite significant increases in gland size. IGF-II mRNA also remained unchanged after unilateral adrenalectomy and decreased after ACTH infusion, to a greater extent than IGF-I mRNA. Liver IGF-I mRNA did not change with ACTH exposure, indicating an effect specific to the adrenal. We also measured adrenal P450scc mRNA as a marker of steroidogenic capacity. P450scc mRNA was unchanged after unilateral adrenalectomy and increased with ACTH infusion. Thus IGF-I and IGF-II mRNAs respond in parallel, but in different fashions with different stimuli for adrenal growth. The decrease in IGF mRNA after exposure to ACTH may be a factor in the ACTH-induced inhibition of compensatory hypertrophy after unilateral adrenalectomy.

Adrenal Glands↗

PubMed1990

Epinephrine exacerbates arthritis by an action at presynaptic B2-adrenoceptors.

Sympathetic efferents contribute to the severity of joint injury in experimental arthritis in the rat, [Levine J. D. et al. (1986) J. Neurosci. 6, 3423-3429] and beta 2-adrenergic receptor antagonists suppress the disease [Levine J. D. et al. (1988) Proc. natn. Acad. Sci. U.S.A. 85, 4553-4556]. The present study was directed at determining the endogenous ligand for, and target of, the beta 2-receptor contribution to arthritis. We report that adrenal medullectomy significantly reduced joint injury in experimental arthritis, but that severe joint injury was re-established in adrenal medullectomized rats chronically treated with epinephrine or the beta 2-agonist, salbutamol. The ability of these two drugs to enhance joint injury in adrenal medullectomized rats was blocked by sympathectomy. These data suggest that adrenal medulla-derived epinephrine acts at beta 2-adrenoceptors on sympathetic efferent nerve terminals, to contribute to the severity of experimental arthritis.

Adrenal Medulla↗

PubMed1990

Decreased sensitivity to glucocorticoid fast feedback in chronically stressed rats.

A number of changes in anterior pituitary corticotrophs occur after chronic footshock. These include increased ACTH and beta-endorphin content and a loss of glucocorticoid negative feedback on corticotropin-releasing hormone (CRH)-stimulated ACTH and beta-endorphin secretion, without changes in sensitivity to ovine CRH examined in vitro. The present studies were undertaken to determine whether the in vitro changes were reflected by similar changes in vivo. We developed a fast feedback paradigm using a 5-min swim stress as challenge, with injection of saline or corticosterone immediately prior to swim. Corticosterone reliably decreased ACTH and beta-endorphin responses to swim over the 30-min period studied. This feedback inhibition did not occur in rats that were either exposed to 30 min of chronic footshock for 7 or 14 days or in rats that were treated with corticosterone daily for 14 days in a regimen that has been reported to decrease hippocampal glucocorticoid receptors. By contrast, in rats exposed to the less intense stimulus of 30 min swim for 14 days, the fast feedback action of corticosterone was intact. These results suggest that both fast and delayed feedback corticosterone-inhibitory mechanisms may be blocked by relatively high levels of chronic stress or by chronic treatment with corticosterone, possibly as a consequence of decreased hippocampal glucocorticoid receptor number.

Adrenocorticotropic Hormone↗

PubMed1990

Induction of fos-like immunoreactivity in hypothalamic corticotropin-releasing factor neurons after adrenalectomy in the rat.

To identify brain sites responding to the removal of corticosterone feedback by adrenalectomy (ADX), rat brains were processed for fos immunocytochemistry 1, 3, and 7 days after ADX, sham-ADX, or no surgery using a polyclonal antiserum to fos residues 132-154. Compared to SHAM, ADX rats exhibited strong fos-like immunoreactivity (FLI) only in the parvocellular neurons of the paraventricular hypothalamic nuclei (PVN) 1, 3, and 7 days after surgery. Replacement with a corticosterone pellet at the time of adrenalectomy (ADX + B) prevented this increase in PVN FLI in three of four rats at 1 day, all rats at 3 days, and two of seven rats 7 days after surgery; 100 micrograms/ml corticosterone in the drinking water for 2 days before perfusion reversed ADX-induced increases in PVN FLI in 7-day ADX rats. Providing 25 micrograms/ml corticosterone in the drinking water to ADX rats for 5 days after surgery did not prevent expression of PVN FLI, even though this dose has been shown to normalize morning basal ACTH levels in ADX rats. Virtually all parvocellular PVN neurons expressing FLI after ADX costained for CRF. Some parvocellular neurons also expressed both fos and vasopressin. In all rats, many brain regions expressed FLI that was not related to adrenalectomy. We conclude that the changes in neuronal FLI correlate with demonstrated changes in neuroendocrine activity after ADX; however, suppression of ADX-induced FLI may require higher replacement levels of corticosterone than inhibition of ADX-induced ACTH secretion.

Adrenalectomy↗

PubMed1990

Fed, but not fasted, adrenalectomized rats survive the stress of hemorrhage and hypovolemia.

We have recently shown that conscious adrenalectomized rats exhibit nearly normal recovery of arterial blood pressure during the 5 h after hemorrhage. In those experiments, it appeared that a previous reduction in food intake might have compromised the recovery of blood pressure and increased mortality. These experiments were designed to test in conscious sham-adrenalectomized (control) and adrenalectomized rats prepared with indwelling arterial and venous cannulae 1) the effects of a 20- to 24-h fast (compared to rats fed ab libitum) on the mobilization of plasma substrates and recovery of arterial blood pressure after a 15 ml/kg.5 min hemorrhage, and 2) vascular responsivity to pressor agents in fed or fasted groups before or 2 h after hemorrhage. In all rats hemorrhage resulted in decreased arterial pressure and heart rate. Arterial pressure recovered to near normal in both fed and fasted control groups and in the fed adrenalectomized rats, and all of these rats survived for 24 h after stress. By contrast, in the fasted adrenalectomized rats, arterial pressure recovered only during the first 1.5-2 h and then failed, resulting in 100% mortality by 3-5 h. Compared to the other three groups, in which substrate levels either increased or remained fairly stable, plasma glucose and beta-hydroxybutyrate concentrations fell steadily from 1.5-2 h after hemorrhage until death occurred in the fasted adrenalectomized rats. Basal ACTH concentrations were elevated compared to control values in both adrenalectomized groups (fed and fasted). Hemorrhage caused increases in plasma ACTH in all groups; the magnitude of the responses did not differ among the groups. The dilution of Evans' blue dye after hemorrhage (used as an index of fluid movement into the vascular space) was not different in control and adrenalectomized rats (either fed or fasted). There were no differences in pressor responses to phenylephrine, vasopressin, or angiotensin-II between the fed and fasted conditions in the control rats either before or after hemorrhage. There was a fasting-associated decrease in vascular responsivity to vasopressin, but normal responsivity to phenylephrine and angiotensin-II, in the adrenalectomized rats both before and after hemorrhage.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗

PubMed1990

Corticosterone, but not glucose, treatment enables fasted adrenalectomized rats to survive moderate hemorrhage.

Fed adrenalectomized rats survive the stress of hemorrhage and hypovolemia, whereas fasted adrenalectomized rats become hypotensive and hypoglycemic after the first 90 min and die within 4 h. We have studied the effects of glucose and corticosterone (B) infusions after hemorrhage as well as treatment with B at the time of adrenalectomy on the capacity of chronically prepared, conscious, fasted, adrenalectomized rats to survive hemorrhage. We have also measured the magnitudes of vasoactive hormone responses to hemorrhage. Maintenance of plasma glucose concentrations did not sustain life; however, treatment of rats at the time of adrenalectomy with B allowed 100% survival, and acute treatment of adrenalectomized rats at the time of hemorrhage allowed about 50% survival during the 5-h posthemorrhage observation period. Rats in the acute B infusion group that died exhibited significantly increased plasma B and significantly decreased plasma glucose concentrations by 2 h compared to the rats that lived. Plasma vasopressin, renin, and norepinephrine responses to hemorrhage were markedly augmented in the adrenalectomized rats not treated with B, and plasma vasopressin concentrations were significantly elevated at 1 and 2 h in all of the rats that subsequently died compared to values in those that lived. We conclude that: 1) death after hemorrhage in fasted adrenalectomized rats is not a result of lack of glucose; 2) chronic and, to an extent, acute treatment of fasted adrenalectomized rats with B enables survival; 3) fasted adrenalectomized rats exhibit strong evidence of hepatic insufficiency which is not apparent in either fed adrenalectomized rats or B-treated fasted adrenalectomized rats; 4) death after hemorrhage in fasted adrenalectomized rats may result from hepatic failure as a consequence of marked splanchnic vasoconstriction mediated by the actions of extraordinarily high levels of vasoactive hormones after hemorrhage; and 5) B appears to act to decrease the magnitude of response of vasoactive hormones after hemorrhage in fasted adrenalectomized rats.

Adrenalectomy↗

PubMed1990

Adrenalectomy in the neonate: adult-like adrenocortical system responses to both removal and replacement of corticosterone.

Neonatal rats exhibit a period of diminished responsiveness to stress between days 3-10 of life, which has been shown to be associated with an increased sensitivity to corticosterone (B) inhibitory feedback. In this study we further investigated B feedback potency on regulation of ACTH by examining 1) the time course of changes in pituitary ACTH secretion and content, plasma B and B-binding globulin (CBG) concentrations, and thymus weight after adrenalectomy (ADX) performed on 5-day-old pups, with or without sc 5% B pellet replacement, and 2) the time required for acute (B injection) and the B dose required for constant (B pellet) inhibition of ACTH secretion in 10-day-old ADX neonates. As in adult rats, ADX in neonates caused an immediate (3 h) large increase (13-fold) in plasma ACTH levels compared to that in sham-operated rats, followed by a decrease by 12 and 24 h after surgery and a further and sustained increase during the next 4 days. Pituitary ACTH stores were diminished in ADX rats by 3, 12, and 24 h and increased thereafter. Five percent B pellet replacement abolished ADX-induced changes in plasma and pituitary ACTH until days 4-5, when plasma ACTH was slowly released from B inhibition (circulating B values were similar to ADX values). By day 10 of life, inhibition of plasma ACTH by calculated free B showed an IC50 of 1.09 nM. Plasma CBG concentrations exhibited a clear developmental pattern in sham-operated rats, being lower on days 6-8 than earlier or later. Typical ADX-induced increases in CBG levels were observed from day 3 on after surgery, at the same time as a transient decrease in CBG levels occurred in ADX plus 5% B rats. On day 10 of age, inhibition of CBG by calculated free B demonstrated an IC50 of 1.5 nM. Although no enlargement of the thymus was observed after neonatal ADX, thymus weight was significantly diminished by 12 h after B replacement and in a dose-related manner at 5 days with B pellets containing 5-25% B. The thymus contained mostly type II glucocorticoid receptors, which did not up-regulate 3 h or 5 days after ADX. Acute sc injection of B (10-34 micrograms/g BW) in 10-day-old rats inhibited ADX-induced ACTH secretion within 30 min, and the estimated half-time for the inhibition was 40 min. By 2 h after B injection, plasma ACTH levels were comparable to those in sham-operated animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗

PubMed1989

Stimulation of rat B-lymphocyte proliferation by corticotropin-releasing factor.

The mitogenic effect of corticotropin-releasing factor (CRF) on rat lymphocytes was investigated. When rat splenocytes were cultured for 48 hr with CFR, a dose-dependent increase in incorporation of 3H-thymidine (3H-Tdr) was observed, with a maximal response at 10 nM CRF. Comparison of the proliferative effect of CRF on enriched populations of B lymphocytes, T lymphocytes, or macrophages revealed that only B lymphocytes responded following treatment with CRF. When lymphocytes derived from different lymphoid tissues were compared, CRF had a greater proliferative effect on lymphocytes derived from gut-associated lymphoid tissue (mesenteric lymph nodes and Peyer's patches) than on lymphocytes from spleen or inguinal lymph nodes; CRF had no effect on thymocytes. Synthetic fragments of CRF were used to determine which portions of the peptide are recognized by lymphocytes. The C-terminal fragments alpha-helical CRF9-41 and CRF21-41 were as potent as native CRF in stimulating B-lymphocyte proliferation, whereas CRF1-20 did not stimulate proliferation. The activity of these peptides suggests that CRF stimulates lymphocyte proliferation by cellular recognition of structural determinants in the C-terminal one-half of the peptide.

Animals↗

PubMed1989

Vascular responsiveness in adrenalectomized rats with corticosterone replacement.

To determine under resting, unstressed conditions the circulating glucocorticoid concentrations that best maintain sensitivity of the vascular smooth muscle and baroreceptor responses to vasoactive agents, rats with vascular cannulas were sham-adrenalectomized (sham) or adrenalectomized (ADRX) and provided with four levels of corticosterone replacement (approximately 100 mg fused pellets of corticosterone: cholesterol 0, 20, 40, and 80% implanted subcutaneously at the time of adrenal surgery). Changes in vascular and baroreflex responses were determined after intravenous injection of varying doses of phenylephrine and nitroglycerin with measurement of arterial blood pressure and heart rate in the conscious, chronically cannulated rats. Vascular sensitivity was decreased, and resting arterial blood pressure tended to be decreased in the adrenalectomized rats; both were restored to normal with levels of corticosterone (40%), which also maintained body weight gain, thymus weight, and plasma corticosteroid binding globulin concentrations at normal values. The baroreflex curve generated from the sham group was different from the curves generated from the ADRX+0, 20, and 40% groups, but not different from that of the ADRX+80% group, suggesting that the baroreflex is maintained by higher levels of corticosterone than are necessary for the maintenance of the other variables. These data demonstrate that physiological levels of corticosterone (40% pellet) restore vascular responsiveness, body weight, thymus weight, and transcortin levels to normal in ADRX rats, whereas higher levels (80% pellet) are necessary for restoration of the baroreflex.

Adrenalectomy↗

PubMed1989

Paraventricular stimulation with glutamate elicits bradycardia and pituitary responses.

The excitatory neurotransmitter, L-glutamate (0.5 M, pH 7.4), or the organic acid, acetate (0.5 M, pH 7.4), was microinjected (50 nl over 2 min) directly into the paraventricular nuclei (PVN) of pentobarbital sodium-anesthetized rats while arterial blood pressure and heart rate and plasma adrenocorticotropic hormone (ACTH), vasopressin, and oxytocin were measured. Activation of PVN neurons with L-glutamate led to increases in plasma ACTH, vasopressin, and oxytocin and a profound bradycardia (approximately 80 beats/min) with little change in arterial blood pressure. Microinjection of acetate had no effect on the above variables. The decrease in heart rate was shown to be dependent on the concentration of glutamate injected and the volume of injectate. The bradycardia was mediated through the autonomic nervous system because ganglionic blockade (pentolinium tartrate) eliminated the response; atropine and propranolol severely attenuated the bradycardia. The bradycardia was greatest when L-glutamate was microinjected into the caudal PVN. Injections into the rostral PVN or into nuclei surrounding the PVN led to small or nonsignificant decreases in heart rate. Focal electric stimulation (2-50 microA) of the PVN also led to decreases in heart rate and arterial blood pressure. These data suggest that activation of PVN neurons leads to the release of ACTH, vasopressin, and oxytocin from the pituitary and a bradycardia that is mediated by the autonomic nervous system.

Adrenocorticotropic Hormone↗

PubMed1989

ACTH secretion and ventilation increase at similar arterial PO2 in conscious rats.

To compare the arterial PO2 (PaO2) at which adrenocorticotropic hormone (ACTH) secretion and ventilation are stimulated, conscious rats with chronic femoral arterial catheters were exposed for 50 min to 21, 18, 15, 12, or 9% O2. Decreases in arterial PCO2 (PaCO2) and increases in arterial pH and adrenocortical system activity occurred consistently throughout the exposure period in rats exposed to 9 or 12% O2. In contrast, changes in PaCO2 or pH were only transient or delayed, plasma ACTH did not change, and plasma corticosterone only increased after 20 min in rats exposed to 15 or 18% O2 relative to those breathing 21% O2. Omitting the large blood sample at 20 min for ACTH eliminated the increase in corticosterone in the 15% O2 group. Overall, ACTH increased, and PaCO2 decreased, below PaO2 of approximately 60 Torr. We conclude that ACTH secretion increases at a similar PaO2 as hyperventilation-induced decreases in PaCO2 and thus represents a primary physiological response to acute hypoxia; hemodynamic stimuli may also interact with hypoxia to augment adrenocortical system activity.

Adrenocorticotropic Hormone↗

PubMed1989

Role of alpha-adrenergic mechanism in effects of morphine on the hypothalamo-pituitary-adrenocortical and cardiovascular systems in the rat.

The role of alpha-adrenergic mechanism in the acute effects of morphine in the hypothalamo-pituitary-adrenocortical (HPA) and cardiovascular (CV) systems, and the interrelationship between the HPA and CV responses to alpha-adrenoceptor antagonists and/or morphine were studied by peripheral administration of prazosin, a selective alpha 1-adrenoceptor antagonist, and yohimbine, a selective alpha 2-adrenoceptor antagonist, in conscious, unstressed or ether-stressed rats. The test substances were administered intravenously or intraperitoneally in chronically cannulated or noncannulated rats. In the i.v. experiment, morphine (1 mg/100 g BW) rapidly induced a pronounced bradycardia and a short-lasting fall in blood pressure (BP), followed by a rise in BP, and increased plasma corticosterone concentration. Prazosin (0.5 mg/kg BW) induced a rapid fall in BP and tachycardia, and increased plasma corticosterone concentration. Pretreatment with prazosin did not block the effect of morphine on the CV system, but abolished the morphine-induced increment in plasma corticosterone concentration. Yohimbine (0.5 mg/kg BW) induced a rapid and a subsequent slowly developing rise in BP and tachycardia, and increased plasma corticosterone concentration. Pretreatment with yohimbine did not block the effect of morphine on the CV system nor alter the stimulatory effect of morphine on the secretion of corticosterone. In the intraperitoneal experiment, morphine (2 mg/100 g BW) stimulated the secretion of adrenocorticotropic hormone (ACTH) and corticosterone and prazosin (1 mg/kg BW) stimulated the secretion of corticosterone, but pretreatment with prazosin reduced the morphine-induced increment in plasma corticosterone concentration in unstressed rats. In stressed rats, morphine reduced the stress-induced increment in plasma ACTH and corticosterone concentrations and prazosin also reduced the stress-induced increment in plasma corticosterone concentration. Pretreatment with prazosin did not alter the inhibitory effect of morphine...

Adrenal Cortex↗

PubMed1989

Correlation between the stress-induced transient increase in corticotropin-releasing hormone content of the median eminence of the hypothalamus and adrenocorticotropic hormone secretion.

Intravenous angiotensin II and ether stress were found to produce a rapid, transient increase in the corticotropin-releasing hormone (CRH) content of the median eminence as measured by a radioimmunoassay employing an antibody against rat CRH(1-41). This confirms previous reports of transient increases in CRH measured by bioassay. The increase did not occur in the paraventricular region or in other parts of the brain. It occurred along with an increase in plasma adrenocorticotropic hormone (ACTH) when a second ether stress was administered 1 h after the first, and it also occurred when rats that had been adrenalectomized for 5 days were exposed to ether. The increases in CHR and the ACTH responses to ether were reduced or abolished by dexamethasone and pentobarbital. Four days after semicircular knife cuts in the posterior hypothalamus, resting CRH in the median eminence was increased but there was no further rise after ether stress. Plasma ACTH was normal at rest after the cuts, but the increase produced by ether was reduced. The ACTH responses to angiotensin II and immobilization were also reduced. Because the posterior knife cuts reduced hypothalamic catecholamine content, the effects of reducing hypothalamic norepinephrine and epinephrine by administration of the dopamine-beta-hydroxylase inhibitor diethyldithiocarbamate (DDC) were tested. Five hours after DDC, plasma ACTH was elevated but there was no further increase with ether stress. The median eminence CRH content was normal but failed to increase after exposure to ether.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗