Biomedical subjects

J Warberg

Publications and source records attributed to J Warberg.

At least 73 records · Page 4Linked to original sources

PubMed1994

Histamine stimulates c-fos expression in hypothalamic vasopressin-, oxytocin-, and corticotropin-releasing hormone-containing neurons.

The stimulatory action of centrally administered histamine (HA) on secretion of the anterior pituitary hormones ACTH, beta-endorphin, and PRL is indirect, and previous studies have suggested that hypothalamic neurons containing CRH, arginine vasopressin (AVP), and oxytocin (OT) are involved in this response. We studied the effect of HA on neuronal activation in the hypothalamus by investigating the expression of c-fos, which is a protooncogene activated early when neurons are stimulated. The expression of c-fos was evaluated by detection of c-fos immunoreactivity (c-fos-IR) using immunohistochemistry and by measurement of c-fos mRNA using in situ hybridization techniques. In addition, the identity of the HA-stimulated neurons was investigated by dual antigen immunohistochemistry visualizing AVP-, OT-, or CRH-IR in the neurons showing increased c-fos expression. HA (270 nmol) infused intracerebroventricularly increased c-fos-IR in the hypothalamus, especially in the periventricular hypothalamic areas and certain hypothalamic nuclei, including the paraventricular nucleus (PVN) and supraoptic nucleus (SON). c-fos-immunoreactive nuclei were observed throughout the SON, whereas in the PVN, c-fos-IR was particularly pronounced in the subnuclei known to contain AVP, OT, and CRH neurons. Double labeling experiments confirmed that c-fos was expressed in AVP-, OT-, and CRH-immunoreactive as well as other neurons. In addition, HA intracerebroventricularly induced a moderate expression of c-fos-IR in the arcuate nucleus. In situ hybridization showed increased levels of c-fos mRNA in both the PVN and SON after HA infusion. We conclude that HA-induced secretion of ACTH, beta-endorphin, and PRL may be mediated via activation of hypothalamic AVP, OT, and CRH neurons.

Animals↗

PubMed1994

Dehydration-induced release of vasopressin involves activation of hypothalamic histaminergic neurons.

The hypothalamic neurotransmitter histamine (HA) induces arginine vasopressin (AVP) release when administered centrally. We studied and characterized this effect of HA with respect to receptor involvement. In addition, we studied the possible role of hypothalamic histaminergic neurons in the mediation of a physiological stimulus (dehydration) for AVP secretion. Intracerebroventricular administration of HA, the H1-receptor agonists 2(3-bromophenyl)HA and 2-thiazolylethylamine, or the H2-receptor agonists amthamine or 4-methyl-HA stimulated AVP secretion. The stimulatory action of HA on AVP was inhibited by pretreatment with the H1-receptor antagonist mepyramine or the H2-receptor antagonist cimetidine. Twenty-four hours of dehydration elevated the plasma osmolality from 298 +/- 3 to 310 +/- 3 mmol/liter and increased the plasma AVP concentration 4-fold. The hypothalamic content of HA and its metabolite tele-methyl-HA was elevated in response to dehydration, indicating an increased synthesis and release of hypothalamic HA. Dehydration-induced AVP secretion was lowered when neuronal HA synthesis was inhibited by the administration of (S) alpha-fluoromethylhistidine or when the animals were pretreated with the H3-receptor agonist R(alpha)methylhistamine, which inhibits the release and synthesis of HA, the H1-receptor antagonists mepyramine and cetirizine, or the H2-receptor antagonists cimetidine and ranitidine. We conclude that HA, via activation of both H1- and H2-receptors, stimulates AVP release and that HA is a physiological regulator of AVP secretion.

Animals↗

PubMed1994

Histaminergic activation of the hypothalamic-pituitary-adrenal axis.

Centrally administered histamine (HA) stimulates the secretion of adenohypophysial POMC-derived peptides, which subsequently cause release of corticosterone. The effect of HA on POMC-derived peptide release is indirect, and it is possible that hypothalamic neurons containing corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), or oxytocin (OT) are involved in the mediation of this response. We studied the effect of HA on: 1) expression of CRH, AVP, and OT messenger RNA (mRNA) at the hypothalamic level; 2) expression of c-fos and POMC mRNA at the pituitary level; and 3) peripheral plasma levels of AVP, OT, ACTH, beta-endorphin (beta-END), and corticosterone. HA (270 nmol) infused intracerebroventricularly increased the expression of CRH, AVP, and OT mRNA in the paraventricular nucleus as well as that of OT mRNA in the supraoptic nucleus of the hypothalamus. At the pituitary level the expression of mRNA for c-fos and POMC increased in the anterior but not in the intermediate lobe in response to HA. Plasma levels of AVP, OT, ACTH, beta-END, and corticosterone all increased in response to central HA administration. Circulating levels of AVP and OT peaked after 5 min, ACTH and beta-END after 15 min, whereas corticosterone levels were highest after 30 min. In concert with our earlier discoveries, the present data support the hypothesis that HA-induced secretion of ACTH and beta-END is mediated via central activation of hypothalamic neuroendocrine neurons containing CRH, AVP, and/or OT.

Animals↗

PubMed1994

Histamine- and stress-induced prolactin secretion: importance of vasopressin V1- and V2-receptors.

We investigated the involvement of arginine vasopressin (AVP) V1- and V2-receptors in the prolactin (PRL) secretory response to histamine (HA) or restraint stress stimulation in conscious male rats by selective blockade of AVP receptors using different antagonists. Histamine (270 nmol) administered intracerebroventricularly or 5 min of restraint stress stimulated PRL secretion 10-14-fold. Pretreatment with the selective V1-receptor antagonists [1-(p-t-butyl-beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-D-arginine]vasopressin or [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-arginine]vassopressin inhibited the PRL response to HA and restraint stress in a dose-dependent manner with maximal inhibition of 60%. The effect of the two antagonists was identical when equipotent antivasopressor doses were administered. The selective V2-receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid)-2-D-isoleucine-4-isoleucine-8-arginine]vasopressin was unable to inhibit the PRL response significantly. Combined administration of the V1-receptor antagonist [1-(p-t-butyl-beta-mercapto-beta, beta-cyclopentamethylene propionic acid-2-(O-methyl)tyrosine-8-D-arginine]vasopressin and the V2-receptor antagonist inhibited the PRL response to HA to the same extent as that observed when the V1-antagonist was administered alone. None of the antagonists used had any effect on basal PRL secretion. We conclude that AVP seems to play a role in the mediation of HA- and restraint stress-induced secretion of PRL, and that the AVP receptor involved is primarily of the V1-type or similar to this.

Animals↗

PubMed1993

Effect of diazepam on endocrine and cardiovascular responses to head-up tilt in humans.

Effects of the GABAergic drug diazepam (0.15 mg kg-1, i.v.) on cardiovascular and endocrine responses to 50 degrees head-up tilt were evaluated in seven men. During the initial phase of tilt (normotensive phase), increases in heart rate (HR) and total peripheral resistance (TPR) and decreases in cardiac output were unaffected by diazepam. Also the associated increase in plasma noradrenaline did not change, while response in plasma ACTH was diminished and in plasma cortisol abolished by diazepam (F(1,10) = 6.45; P < 0.03). After 42 +/- 4 min of sustained tilt with saline (control) and 47 +/- 6 min (n.s.) after diazepam, presyncopal symptoms appeared (hypotensive phase) associated with decreases in HR, MAP, and TPR (P < 0.01). This episode induced a 2-3-fold increase in plasma ACTH, beta-endorphin, prolactin, cortisol (< 0.01), and a moderate increase in plasma adrenaline (P < 0.05). Diazepam did not significantly change cardiovascular and endocrine responses to the hypotensive phase of tilt. Results indicate that diazepam attenuates the cortisol part of pituitary-adrenal responses to moderate, but not to severe, central hypovolaemia in humans with no effect on cardiovascular tolerance.

Adult↗

PubMed1993

Effect of serotonin receptor blockade on endocrine and cardiovascular responses to head-up tilt in humans.

Effects of blockade of serotonin (5-HT) receptors on the integrated cardiovascular and endocrine adaptations during head-up tilt were investigated in normal men. In control experiments 50 degrees head-up tilt increased heart rate (HR), total peripheral resistance (TPR), plasma renin activity (PRA) and sympathetic activity (plasma noradrenaline; NA). A moderate increase in pituitary-adrenal hormones (plasma ACTH, beta-END and cortisol) was observed. After a mean tilt time of 30 +/- 5 min (n = 20) presyncopal symptoms associated with decreases in HR, TPR and arterial pressure occurred. At this time pituitary hormones, cortisol, adrenomedullary (plasma adrenaline; A) as well as vagal activity (plasma pancreatic polypeptide) were markedly increased, whereas sympathetic activity (plasma NA) decreased. The 5-HT1+2 receptor antagonist methysergide did not significantly interfere with cardiovascular variables but attenuated the response of NA, prolactin (PRL), beta-endorphin (beta-END) and PRA (P < 0.02). The 5-HT2-receptor antagonist ketanserin reduced the tolerated tilt time (10 +/- 4 vs. 32 +/- 2 min; P < 0.0003, n = 7) but had no significant effects on hormonal variables. The 5-HT3-receptor antagonist ondansetron abolished the adrenomedullary response to hypotension without affecting cardiovascular tolerance or the activity of the pituitary-adrenal axis. The results suggest that serotonergic mechanisms may be involved in the integrated cardiovascular and endocrine responses to central blood volume depletion in humans.

Adrenocorticotropic Hormone↗

PubMed1993

Enhanced heart rate response to haemorrhage by ileus in the pig.

Effects of ileus on cardiovascular and hormonal responses to haemorrhage were evaluated in 10 anaesthetized pigs. Ileus was induced and the bleeding sequence repeated on the following day. Before ileus, a resting heart rate (HR) of 105 (range 83-140) beats min-1 remained unchanged until haemorrhage amounted to 15% of the blood volume. With a blood loss of 28% HR increased to a maximum of 162 (126-245) beats min-1. In contrast, ileus increased HR upon initiation of haemorrhage from a similar resting value to a maximum of 200 (152-250) beats min-1 (P < 0.0005). There were neither statistical differences in mean arterial pressure, cardiac output, central venous pressure, thoracic electrical impedance, pulmonary arterial mean pressure, pulmonary wedge pressure, pulmonary and systemic vascular resistances, nor in plasma concentrations of dopamine, adrenaline, vasopressin and aldosterone during haemorrhage before and after ileus. Plasma noradrenaline increased more with haemorrhage after than before ileus: from 2.8 (1.2-5.0) to 13 (2.3-59.0) vs. 3.0 (1.5-4.2) to 3.6 (2.7-17.5) nmol l-1 (P < 0.005). Also, the pancreatic polypeptide response to haemorrhage was enlarged with ileus (29 (0-60) to 90 (45-145) vs. 23 (0-64) to 57 (27-106) pmol l-1 (P < 0.005)). No significant differences could be detected in cardiovascular and hormonal responses to haemorrhage before and after a sham-operation in three pigs. Results demonstrate an immediate and enhanced HR response to haemorrhage in the pig with ileus, reflected in sympathetic activation as indicated by plasma noradrenaline.

Animals↗

PubMed1993

Human circulatory and thermoregulatory adaptations with heat acclimation and exercise in a hot, dry environment.

1. Heat acclimation was induced in eight subjects by asking them to exercise until exhaustion at 60% of maximum oxygen consumption rate (VO2) for 9-12 consecutive days at an ambient temperature of 40 degrees C, with 10% relative humidity (RH). Five control subjects exercised similarly in a cool environment, 20 degrees C, for 90 min for 9-12 days; of these, three were exposed to exercise at 40 degrees C on the first and last day. 2. Acclimation had occurred as seen by the increased average endurance from 48 min to 80 min, the lower rate of rise in the heart rate (HR) and core temperature and the increased sweating. 3. Cardiac output increased significantly from the first to the final heat exposure from 19.6 to 21.4 l min-1; this was possibly due to an increased plasma volume and stroke volume. 4. The mechanism for the increased plasma volume may be an isosmotic volume expansion caused by influx of protein to the vascular compartment, and a sodium retention induced by a significant increase in aldosterone. 5. The exhaustion coincided with, or was elicited when, core temperature reached 39.7 +/- 0.15 degrees C; with progressing acclimation processes it took progressively longer to reach this level. However, at this point we found no reduction in cardiac output, muscle (leg) blood flow, no changes in substrate utilization or availability, and no recognized accumulated 'fatigue' substances. 6. It is concluded that the high core temperature per se, and not circulatory failure, is the critical factor for the exhaustion during exercise in heat stress.

Acclimatization↗

PubMed1993

Arterial pulse pressure and vasopressin release in humans during lower body negative pressure.

The hypothesis was tested that narrowing of arterial pulse pressure (PP) is a determinant of arginine vasopressin (AVP) release in humans. Six normal males completed a two-step lower body negative pressure (LBNP) protocol of -20 and -50 mmHg, respectively, for 10 min each. None of these subjects experienced presyncopal symptoms. Arterial plasma AVP and plasma renin activity (PRA) (at 2-min intervals) only increased subsequent to a decrease in PP (invasive brachial arterial measurements) and stroke volume (ultrasound Doppler technique, n = 4). Simultaneously, mean arterial pressure did not change. A selective decrease in central venous pressure and left atrial diameter (echocardiography, n = 4) at LBNP of -20 mmHg did not affect AVP or PRA, whereas arterial plasma norepinephrine increased (n = 4). During LBNP, significant (P < 0.05) intraindividual linear correlations were observed between log(AVP) and PP in four of the subjects with r values from -0.75 to -0.99 and between log(PRA) and PP in all six subjects with r values from -0.89 to -0.98. In conclusion, these results are in compliance with the hypothesis that narrowing of PP in humans during central hypovolemia is a determinant of AVP and renin release.

Adult↗

PubMed1993

Volume-homeostatic mechanisms in humans during a 12-h posture change.

On one day six male subjects underwent an upright seated (SEAT) study, and on another day they were subjected to a head-down tilt of 3 degrees (HDT). Compared with SEAT, HDT induced prompt increases in central venous pressure (CVP) from -0.5 +/- 0.8 to 8.3 +/- 0.3 mmHg (P < 0.001) and in arterial pulse pressure of 8-18 mmHg (P < 0.001). CVP stabilized after 6 h at levels 2.4-2.8 mmHg below the peak value. Simultaneously, renal sodium excretion gradually increased over the initial 5 h of HDT and stabilized at a level approximately 125 mumol/min over that of SEAT (P < 0.001). Urine flow rate and solute free water clearance increased during the initial 2-6 h of HDT (P < 0.001) but returned to the level of SEAT thereafter. We concluded that CVP is slightly reduced over 12 h of HDT and that a clear temporal dissociation exists between renal sodium and water handling. We suggest that the combined effect of the sustained suppressions of plasma renin activity and plasma aldosterone and norepinephrine concentrations constitutes a mechanism of the increase in renal sodium excretion.

Adult↗

PubMed1993

Involvement of vasopressin in histamine- and stress-induced prolactin release: permissive, mediating or potentiating role?

Arginine vasopressin (AVP) appears to be involved in the histamine (HA)- and stress-induced prolactin (PRL) release. The present investigation was performed in male rats to clarify whether the role of AVP in HA- and restraint stress-induced secretion of PRL is mediating (i.e., the effect of HA or stress is transmitted via AVP) or permissive (i.e., the presence of AVP is required to obtain a stimulatory effect of HA or stress on PRL secretion). Furthermore, we studied whether AVP possessed a potentiating effect on the HA- or stress-induced PRL release. PRL secretion was stimulated 14- to 17-fold by intracerebroventricular infusion of HA (270 nmol) or by 5 min of restraint stress. These effects were inhibited about 80% by immunoneutralization of endogenous AVP with a specific AVP antiserum (abAVP). When specific AVP V1- or V2-receptor agonists, which were not bound by the AVP antiserum, were administered intravenously together with the AVP antiserum, the PRL response to HA or restraint stress was partly (> 50%) reestablished. This effect was observed at low (1.2 or 0.1 nmol) as well as high (3.8 or 0.4 nmol) doses of agonists and when these were administered alone or in combination. In non-immunoneutralized animals, separate administration of agonists at low or high doses as well as combined administration of agonists at low doses had no or only a minor effect on PRL secretion, while combined administration of V1- and V2-agonist in high doses stimulated PRL secretion 6-fold. Taken together, these observations indicate that AVP has a permissive role.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of selective serotonin receptor agonists on prolactin secretion in male rats.

The effect of different serotonin (5-HT) receptor agonists on the release of prolactin (PRL) was investigated in conscious male rats. The 5-HT1 receptor agonists 5-carboxamidotryptamine and RU 24969 stimulated the PRL secretion dose dependently. RU 24969 possessed almost the same potency and efficacy (maximal effect) as 5-HT, while 5-carboxamidotryptamine was more potent and had a higher efficacy. The 5-HT1 + 2 receptor agonist MK 212 stimulated the PRL secretion only at high doses. The 5-HT2 receptor agonist S(alpha)methyl-5-HT and the 5-HT3 receptor agonist 2-methyl-5-HT had minor or no effect on the PRL secretion. The PRL-releasing effect of submaximal doses of 5-carboxamidotryptamine and RU 24969 was blocked by the 5-HT1 + 2 receptor antagonist methysergide and enhanced by other 5-HT agonists, but was unaffected by the 5-HT2 and 5-HT3 receptor antagonists. MK 212, S(alpha)methyl-5-HT, and--in particular--2-methyl-5-HT potentiated the effect of 5-carboxamidotryptamine. Likewise, 2-methyl-5-HT potentiated the effect of RU 24969, while MK 212 or S(alpha)methyl-5-HT had an additive to slightly potentiating effect. The findings show that 5-HT stimulates PRL secretion via 5-HT1 as well as 5-HT2 receptors and that activation of 5-HT2 and 5-HT3 receptors significantly augment the PRL-stimulating effect of 5-HT1 receptor activation. This indicates that the 5-HT receptor subtypes may interact functionally in the mediation of the PRL-releasing effect of the serotonergic system.

Animals↗

PubMed1993

Involvement of vasopressin V1- and V2-receptors in histamine-and stress-induced secretion of ACTH and beta-endorphin.

Arginine-vasopressin (AVP) seems to be involved in the histamine (HA)-and stress-induced release of ACTH and beta-endorphin (beta-END). We studied the effect of selective AVP V1-or V2-receptor blockade on the ACTH and beta-END response to HA or restraint stress in conscious male rats. HA (270 nmol) administered intracerebroventricularly or 5 min of restraint stress caused a 3-to 7-fold increase in the plasma levels of ACTH and beta-END immunoreactivity (beta-ENDir). Pretreatment of the animals with the nonselective V1+2-receptor antagonist [1-Pmp-2-D-Phe-4-Ile-8-Arg]vasopressin, which was administered intravenously in a low (23 nmol) or a high dose (90 nmol) inhibited the HA-or restraint stress-induced secretion of ACTH and beta-ENDir 60 and 25-70%, respectively. Pretreatment with equipotent doses of the selective V1-receptor antagonist [1-(p-tBu)Pmp-2-Tyr(O-Me)-8-D-Arg]vasopressin (25 nmol) and/or the selective V2-receptor antagonist [1-Pmp-2-D-Ile-4-Ile-8-Arg]vasopressin (7.0 nmol) attenuated the response of ACTH and beta-ENDir to HA or restraint stress by 60-80 and 40-60%, respectively. In general, these doses of antagonists had no effect on basal hormone levels. We conclude that AVP takes part in the mediation of HA- and restraint stress-induced ACTH and beta-END secretion. This effect seems to be mediated via both AVP V1- and V2-receptors or a less selective receptor with ligand specificity for both V1- and V2-receptor antagonists.

Adrenocorticotropic Hormone↗

PubMed1993

Responses of anterior pituitary hormones and hypothalamic histamine to blockade of histamine synthesis and to selective activation or inactivation of presynaptic histamine H3 receptors in stressed rats.

The stress-induced release of anterior pituitary hormones and changes in hypothalamic content of histamine (HA) and its metabolite tele-methylHA (t-meHA) were studied in male rats during inhibition of HA synthesis or activation or blockade of HA H3 receptors. Pretreatment with the HA synthesis inhibitor alpha-fluoromethylhistidine (alpha-FMH; 200 micrograms intracerebroventricularly (icv) at -120 min) or the specific H3 receptor agonist R(alpha)methylhistamine (RmHA; 10 mg/kg intraperitoneally (ip) at -180 and -60 min) inhibited by 30-80% the responses of prolactin (PRL), corticotropin (ACTH) and beta-endorphin (beta-END) immunoreactivity to 1, 2.5 or 5 min of restraint stress (p < 0.05-0.01), but had no effect on basal secretion of the hormones. The inhibitory effect of the H3 receptor agonist RmHA (10 mg/kg x 2) on the hormone response to 5 min of restraint stress was prevented by simultaneous ip administration of the H3 receptor antagonist thioperamide. alpha-FMH reduced the hypothalamic content of HA 60% and that of t-meHA 30%, while RmHA had no effect on the HA content. Restraint stress for 5 min did not affect the HA and t-meHA contents, which may be due to the short duration of stress exposure. Pretreatment with the H3 receptor antagonist thioperamide (5 or 10 mg/kg ip at -120 min) had no effect on basal or restraint stress-induced release of PRL, ACTH or beta-END, although the compound increased the hypothalamic content of t-meHA 2-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1993

Impaired histamine- and stress-induced secretion of ACTH and beta-endorphin in vasopressin-deficient Brattleboro rats.

Arginine vasopressin (AVP), corticotropin-releasing hormone (CRH) and catecholamines seem to be involved in the histamine- (HA) and/or stress-induced release of the pro-opiomelanocortin-derived peptides adrenocorticotropic hormone (ACTH) and beta-endorphin (beta-END). The AVP component of the regulatory mechanism can be specifically studied in Brattleboro rats which lack AVP. These animals may therefore serve as a useful biological model for investigating the importance of AVP in the ACTH and beta-END response to HA and stress. On this background, we studied the ACTH and beta-END response to HA or restraint stress in conscious, male dizygotic AVP-deficient Brattleboro rats (DI) and compared the hypothalamic content of CRH and catecholamines in these rats with that of nondiabetic isogenic Long-Evans rats (LE). In addition, we studied the hypothalamic AVP content in LE rats after HA infusion or exposure to restraint stress. HA (270 nmol) administered intracerebroventricularly (i.c.v.) or 5 min of restraint stress caused a 6- to 7-fold increase in plasma concentrations of ACTH and beta-END in LE rats but only a 2- to 3-fold increase in DI rats (p < 0.01 vs. LE). The basal hypothalamic content of CRH and catecholamines (epinephrine, norepinephrine, and dopamine) was similar in DI and LE rats. The hypothalamic AVP content in LE rats was unaffected by central HA infusion or restraint stress and was undetectable in DI rats. We conclude that inherited lack of AVP impaired the ACTH and beta-END response to central HA administration as well as to restraint stress, suggesting that AVP is important for the mediation of these responses.

Adrenocorticotropic Hormone↗

PubMed1993

Permissive, mediating and potentiating effects of vasopressin in the ACTH and beta-endorphin response to histamine and restraint stress.

We investigated in conscious, male rats (1) whether the role of arginine-vasopressin (AVP) in histamine (HA)- and/or restraint stress-induced stimulation of ACTH and beta-endorphin (beta-END) secretion is mediating and/or permissive and (2) whether AVP possesses a potentiating effect on HA- or stress-induced release of ACTH and beta-END. Administration of a specific V1 receptor agonist stimulated ACTH and beta-END secretion dose-dependently while a V2 receptor agonist had no stimulating effect. ACTH and beta-END secretion was stimulated 2- to 3-fold by intracerebroventricular (i.c.v.) infusion of HA (270 nmol) or by 5 min of restraint stress. These effects were inhibited approximately 80% by immunoneutralization of endogenous AVP using a specific AVP antiserum. When the 'AVP tone' was restored in immunoneutralized animals by administration of the specific AVP V1 receptor agonist, which was not bound by the AVP antiserum and had no ACTH and beta-END-releasing effect in the dose used, the ACTH and beta-END response to HA or restraint stress was almost completely reestablished. The specific AVP V2 receptor agonist, which was not bound by the AVP antiserum, reestablished only in part the response of ACTH and beta-END to HA or restraint stress in immunoneutralized animals. AVP administered in doses which had no or minimal ACTH or beta-END releasing effect in itself enhanced the ACTH or beta-END response to submaximal stimulation with HA or restraint stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1993

Insulin/hypoglycemia-induced adrenocorticotropin and beta-endorphin release: involvement of hypothalamic histaminergic neurons.

We have previously found that histamine (HA) is involved in the mediation of restraint- and ether stress-induced release of the POMC-derived peptides ACTH and beta-endorphin (beta-END). In the present study we investigated the possible involvement of hypothalamic histaminergic neurons in the mediation of insulin/hypoglycemia-induced release of ACTH and beta-END in conscious male rats. To do so, hypoglycemia stress was performed during 1) inhibition of HA synthesis, 2) activation of inhibitory presynaptic HA H3-auto-receptors, or 3) blockade of postsynaptic HA H1- or H2-receptors. Hypoglycemia (plasma glucose, 2.2 +/- 0.3 nmol) induced by insulin (3 IU/kg, ip) caused a 3- to 5-fold increase in the plasma concentrations of ACTH and beta-END. A negative exponential correlation was found between the plasma glucose concentration and the ACTH and beta-END levels. Pretreatment of the animals with the HA synthesis inhibitor alpha-fluoromethylhistidine (1.0 mumol) intracerebroventricularly (icv) in a lateral ventricle, inhibited the ACTH and beta-END responses to insulin/hypoglycemia by 60%. When administered ip (100 mumol/kg), the synthesis inhibitor decreased the beta-END response 50%, but did not affect ACTH secretion significantly. Pretreatment of the rats with the H3-receptor agonist R(alpha)methylhistamine (50 mumol/kg, ip, twice) inhibited the secretory responses of ACTH and beta-END to insulin/hypoglycemia by 60-80%. This inhibitory effect of R(alpha)methylhistamine was reversed by prior administration of the specific H3-receptor antagonist thioperamide. Administration of the H1-antagonists mepyramine and cetirizine dose-dependently inhibited the ACTH and beta-END responses to insulin/hypoglycemia, with the highest dose (mepyramine, 350 nmol, icv; cetirizine, 40 mumol/kg, ip) inhibiting the response by 80-100%. The H1-antagonist SKF-93944 (226 nmol, icv) inhibited the ACTH response, but had no effect on the beta-END response. Administration of the H2-antagonists cimetidine (400 nmol, icv) and ranitidine (400 nmol, icv) inhibited the ACTH and beta-END responses to insulin/hypoglycemia by 50-80%. We conclude that histaminergic neurons are involved in the mediation of the insulin/hypoglycemia-induced release of ACTH and beta-END and that the effect is mediated via activation of primarily postsynaptic H1-receptors and, to a lesser extent, H2-receptors.

Adrenocorticotropic Hormone↗

PubMed1992

Reduced left ventricular diameters at onset of bradycardia during epidural anaesthesia.

Pathophysiologic mechanisms of bradycardia during epidural anaesthesia (L3-L4 with 1% lidocaine, 38 ml) were evaluated by studying changes in selected cardiovascular and hormonal parameters. Six of eight subjects (analgesia to T8-T10) remained circulatory stable with no significant changes in heart rate (HR), mean arterial pressure (MAP) and thoracic impedance (TI). In one of two subjects MAP decreased after 25 min from 85 to 50 mmHg (11.3 to 6.7 kPa), HR from 80 to 45 beats.min-1 while thoracic impedance increased from 25.5 to 26.5 ohm. End-systolic diameter (ESD) and end-diastolic diameter (EDD) of the left ventricle determined with echocardiography were reduced from 3.8 to 3.2 cm (17%) and 5.6 to 5.0 cm (11%), respectively. In the other subject MAP decreased after 25 min from 75 to 50 mmHg (10.0 to 6.7 kPa) and HR from 82 to 60 beats.min-1 while thoracic impedance increased from 28.8 to 29.6 ohm. ESD was reduced from 3.8 to 3.3 cm (13%), and EDD from 5.6 to 5.0 cm (11%). Both subjects recovered after infusion of saline and being placed in the head-down position. There were no consistent changes in plasma catecholamines, whereas pancreatic polypeptide increased from 5 and 3 to 152 and 69 pmol.l-1, vasopressin from 3 and 2 to 152 and 46 pmol.l-1, and aldosterone from 282 and 229 to 383 and 485 pmol.l-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗