Plasma vasopressin, growth hormone and ACTH responses to static handgrip in healthy subjects

Ten healthy male subjects took part in the study. They performed three consecutive bouts of static handgrip at 30% of maximal voluntary contraction (MVC), using two hands alternately and without rest intervals. Blood pressure was measured every 30 s and ECG was recorded continuously. Blood samples for arginine vasopressin (AVP), growth hormone (GH), adrenocorticotrophic hormone (ACTH) and cortisol determinations were taken at rest, after each exercise bout, as well as at 10 and 30 min after the last one. During the whole period of exercise (9 min) blood pressure and heart rate were elevated. The effort caused a significant increase in the plasma AVP concentration. In the majority of subjects the peak values occurred after the first or second exercise bout and were followed by a rapid decline of the hormone concentration. Changes in GH, ACTH and cortisol concentrations were insignificant; however, in seven of the ten subjects, considerably elevated plasma GH levels were found at the end of the third exercise bout and/or 10 min after its cessation.     

Dissociation of plasma cortisol and ACTH responses to dexamethasone in healthy subjects

We examined the plasma cortisol and ACTH concentrations after graded doses of dexamethasone in a group of young, healthy adults. The decrease in cortisol was uniform in all subjects, and in 8 subjects there was a high degree of correspondence with the plasma ACTH concentration. The remaining 5 subjects had no change in plasma ACTH concentration during dexamethasone administration. All subjects had an expected diurnal change in cortisol on 2 pretreatment days and there was a corresponding diurnal change in ACTH for those subjects who had associated ACTH and cortisol responses after dexamethasone, while those with dissociated ACTH and cortisol after dexamethasone had no diurnal ACTH pattern. These findings were consistent with the 24-hour pattern of ACTH and cortisol before and after 1.0 mg of dexamethasone in 2 of the same subjects. These results are further evidence for ACTH independent regulation of adrenal function and indicate that pituitary-adrenal regulation in man is more complex than the traditional model of ACTH-cortisol feedback would predict.     

Behavioral and biochemical responses of mice to the intraventricular administration of ACTH analogs and lysine vasopressin.

ACTH_1?24, ACTH_4?10, ACTH_4?10(D-phe), lysine vasopressin (LVP) or an amino acid mixture were administered to mice using bilateral intraventricular injections (5×10^?9 moles per mouse). Behavioral observations were made for the subsequent 85 minutes, and the incorporation of subcutaneously injected [³H]lysine into brain proteins assayed for the last 10 minutes of this period. Mice injected with ACTH_1?24 showed the previously reported stretching and yawning syndrome, an effect also observed with ACTH_4?10(D-phe) but less often. These same peptides also induced a pronounced increase in the proportion of time mice spent grooming. LVP caused a dramatic hyperactivity; mice so injected moved continously about the cage occasionally eating or grooming, but were never still. Injection with ACTH_1?24 or ACTH_4?10(D-phe), but not ACTH_4?10 or LVP, caused significant increases in the incorporation of [³H]lysine into brain protein.     

ACTH,cortisol and glucose responses after administration of vasopressin in cattle and sheep

The present study compared the effects of vasopressin on plasma concentrations of corticotropin, cortisol and glucose in cattle and sheep. After intravenous injection of 1, 0.1 and 0.01 g vasopressin per kg body weight, the plasma vasopressin concentration increased proportionally to the injected dose, and this increase was similar in cattle and sheep. Doses of 1 and 0.1 g per kg body weight of vasopressin triggered significant responses of corticotropin, cortisol and glucose in cattle and sheep. The corticotropin response to both doses was significantly greater in sheep, whereas the glucose response was greater in cattle. The cortisol response did not differ between species. The lowest dose of vasopressin (0.01 g per kg body weight) still induced a significant cortisol response without a substantial effect on plasma corticotropin, suggesting that a direct action of vasopressin on the adrenals may contribute to the observed cortisol response. The results demonstrate that vasopressin increases plasma levels of corticotropin, cortisol and glucose in cattle, as it does in sheep, but the intensities of the corticotropin and glucose responses to vasopressin differ between cattle and sheep. The reasons for these differences remain to be clarified.Abbreviations ACTH corticotropin - AVP vasopressin - bw body weight     

Role of arginine vasopressin in control of ACTH and LH release during stress

To determine the role of arginine vasopressin (AVP) in stress-induced release of anterior pituitary hormones, AVP antiserum or normal rabbit serum (NRS) was micro-injected into the 3rd ventricle of freely-moving, ovariectomized (OVX) female rats. A single 3 microliter injection was given, and 24 hours later, the injection was repeated 30 min prior to application of ether stress for 1 min. Although AVP antiserum had no effect on basal plasma ACTH concentrations, the elevation of plasma ACTH induced by ether stress was lowered significantly. Plasma LH tended to increase following ether stress but not significantly so; however, plasma LH following stress was significantly lower in the AVP antiserum-treated group than in the group pre-treated with NRS. Ether stress lowered plasma growth hormone (GH) levels and this lowering was slightly but significantly antagonized by AVP antiserum. Ether stress also elevated plasma prolactin (Prl) levels but these changes were not significantly modified by the antiserum. To evaluate any direct action of AVP on pituitary hormone secretion, the peptide was incubated with dispersed anterior pituitary cells for 2 hours. A dose-related release of ACTH occurred in doses ranging from 10 ng (10 p mole)-10 micrograms/tube, but there was no effect of AVP on release of LH. The release of other anterior pituitary hormones was also not affected except for a significant stimulation of TSH release at a high dose of AVP. The results indicate that AVP is involved in induction of ACTH and LH release during stress. The inhibitory action of the AVP antiserum on ACTH release may be mediated intrahypothalamically by blocking the stimulatory action of AVP on corticotropin-releasing factor (CRF) neurons and/or also in part by direct blockade of the stimulatory action of vasopressin on the pituitary. The effects of vasopressin on LH release are presumably brought about by blockade of a stimulatory action of AVP on the LHRH neuronal terminals.     

Arterial baroreceptors control plasma vasopressin responses to graded hypotension in conscious dogs

We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.     

Running training attenuates the ACTH responses in rats to swimming and cage-switch stress.

The present study was carried out to investigate the effect of running training on adrenocorticotrophic hormone (ACTH) response in rats to swimming or cage-switch stress to determine whether, after physical training, a cross-adaptation develops in the ACTH responses induced by different types of stresses. Rats were trained by two different kinds of exercises and for two different periods of training: 1) swimming for 4 wk (4W-swimming), 2) running for 4 wk (4W-running), and 3) running for 10 wk (10W-running). Remaining rats were used for control for 4 wk (4W-control) and 10 wk (10W-control). The ACTH response induced by swimming stress was reduced after training by swimming (62.4%) or by running (13.8-16.4%). These training periods also attenuated the ACTH response induced by cage-switch stress (62.4% in the swimming group, 23.8-34.6% in the running groups). After swimming stress, the 4W-swimming and 10W-running groups showed smaller increases in blood glucose than the control groups. In addition, the increased levels of blood lactate in all the trained rats were significantly smaller than those in the control groups, suggesting that an adaptation was achieved after physical training. These results suggest that after running training, cross-adaptation is developed in the ACTH response induced by different types of physical (swimming) or psychological (cage-switch) stresses.     

Systolic pressure predicts plasma vasopressin responses to hemorrhage and vena caval constriction in dogs

We have proposed that the reflex increase in arginine vasopressin (AVP) secretion in response to hypovolemia is due to arterial baroreceptor unloading. If arterial pressure is the key to the mechanism, the slope relating plasma AVP to arterial pressure should be the same in response to hemorrhage, a model of true hypovolemia, and in response to thoracic inferior vena caval constriction (IVCC), a model of central hypovolemia. We tested this hypothesis in conscious, chronically instrumented dogs (n = 8). The mean coefficient of determination (r(2)) values obtained from the individual regressions of log AVP onto systolic pressure (SP) and mean arterial pressure (MAP) in response to hemorrhage were 0.953 +/- 0.009 and 0.845 +/- 0.047, respectively. Paired comparisons indicated a significant difference between the means (P < 0.05), hence, SP was used in subsequent analyses. The mean slopes relating the log of plasma AVP to SP in response to hemorrhage and IVCC were -0.034 +/- 0.003 and -0.032 +/- 0.002, respectively, and the means were not significantly different (P = 0.7). The slopes were not altered when the experiments were repeated during acute blockade of cardiac receptors by intrapericardial procaine. Finally, sinoaortic denervation (n = 4) markedly reduced the slope in both the hemorrhage and IVCC treatments. We conclude that baroreceptors monitoring arterial pressure provide the principal reflex control of AVP secretion in response to hypovolemia.     

ACTH and glucocorticoid responses under two conditions of stress in macaques

Female macaques were tested under two different psychologically stressful situations in which plasma ACTH and glucocorticoid concentrations were measured. In the first, animals were operantly trained to enter a small transport cage over a four-week period, and plasma ACTH and glucocorticoids were measured in response to brief confinement in the cage before and after training. ACTH values were significantly lower in the pre-test (stress) condition when compared to those for the post-test, whereas the opposite result was found for glucocorticoid values. In the second experiment, blood samples were collected before and one hour after exposure to more acute and severe stress (restraint, venipuncture, handcapture, transport). Both ACTH and glucocorticoid values were significantly elevated from baseline at the post-test sample. The differential relationship between the two hormones among the two experiments was likely the result of the specific timing and magnitude of the stress imposed by each test situation.     

Effect of cyclooxygenase inhibitors on the vasopressin induced ACTH and corticosterone response during crowding stress.

The aim of the present study was to compare the effect of social stress on the corticotropin releasing hormone (CRH) and arginine vasopressin (AVP)-induced pituitary-adrenocortical activity. Also the significance of prostaglandins (PG) generated by constitutive and inducible cyclooxygenase (COX-1 and COX-2) in the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by AVP under basal and crowding stress conditions was investigated. The control rats were housed 7 in a standard cage and stressed rats were crowded 24 in a cage of the same size during 7 days. The activity of HPA axis was determined by measuring plasma ACTH and serum corticosterone levels 1 h after i.p. AVP administration. Indomethacin (2.0 mg/kg i.p.), a non-selective COX inhibitor, piroxicam (0.2, 2.0, and 5.0 mg/kg), a more potent COX-1 than COX-2 inhibitor, and compound NS-398 (0.2 and 2.0 mg/kg) a selective COX-2 inhibitor, were administered i.p. 15 min prior to AVP (5.0 microg/kg i.p.) to control or crowded rats. The obtained results indicate that social stress for 7 days considerably inhibits the stimulatory action of AVP on ACTH secretion, while it intensifies the CRH-induced ACTH secretion. Indomethacin, piroxicam and NS-398 significantly diminished the AVP-elicited ACTH and corticosterone secretion in non-stressed rats. None of these COX antagonist induced any significant inhibition of the AVP-induced ACTH and corticosterone secretion in stressed rats. Therefore, PG generated by COX-1 or COX-2 do not participate to a significant extent in the HPA stimulation by AVP during crowding stress. These results suggest that social crowding stress desensitizes the PG stimulatory mechanism which considerably mediates the AVP-induced HPA stimulation under basal conditions. The results contrast with a lack of any involvement of PG in the CRH-induced stimulation of HPA response under basal or crowding stress conditions.     

Beta-endorphin and ACTH in plasma: effects of physical and psychological stress

The effects of the expectancy of an official race (22000 m) and the performance of this last event on plasma levels of beta-Endorphin (B-End) and ACTH have been assessed. In a group of nine athletes, samples were obtained first in basal conditions; second in the day of the run before the warming up period and third after running. B-End immunoactivity was increased from 15.7 +/- 2.0 pg/ml to 23.4 +/- 2.5 pg/ml before the run and up to 30.6 +/- 2.9 pg/ml after the trial. ACTH levels were increased from 8.4 +/- 1.2 pg/ml to 17.9 +/- 2.3 pg/ml before running and up to 36.2 +/- 3.9 pg/ml after running. The results suggest that psychological and physical stress act synergically to increase the levels of B-End and ACTH during the practice of physical exercise.     

Menstrual status and plasma vasopressin, renin activity, and aldosterone exercise responses

The effects of menstrual cycle phase (early follicular vs. midluteal) and menstrual status (eumenorrhea vs. amenorrhea) on plasma arginine vasopressin (AVP), renin activity (PRA), and aldosterone (ALDO) were studied before and after 40 min of submaximal running (80% maximal O2 uptake). Eumenorrheic runners were studied in the early follicular and midluteal phases determined by urinary luteinizing hormone and progesterone and plasma estradiol and progesterone assays; amenorrheic runners were studied once. Menstrual phase was associated with no significant differences in preexercise plasma AVP or PRA, but ALDO levels were significantly higher during the midluteal phase than the early follicular phase. Plasma AVP and PRA were significantly elevated at 4 min after the 40-min run in the eumenorrheic runners during both menstrual phases and returned to preexercise levels by 40 min after exercise. Plasma ALDO responses at 4 and 40 min after exercise were higher in the midluteal phase than the early follicular phase. Menstrual status was associated with no significant differences in preexercise AVP or PRA; however, ALDO levels were significantly higher in the amenorrheic runners. After exercise, responses in the amenorrheic runners were comparable with the eumenorrheic runners during the early follicular phase. Thus, submaximal exercise elicits significant increases in plasma AVP and PRA independent of menstrual phase and status. However, plasma ALDO is significantly elevated during the midluteal phase, exercise results in a greater response during this menstrual phase, and amenorrheic runners have elevated resting levels of ALDO.     

Systemic responses to prolonged hemorrhagic hypotension

Studies are needed to provide a rigorous examination of the relevance of monitored variables during prolonged hemorrhagic hypotension (HH). This study was designed to investigate the parameters that describe biochemical and O2 transport patterns in animals subjected to HH. Systemic parameters that could differentiate survivors from nonsurvivors were identified. An aortic flow probe was implanted in rats (n = 21) for continuous measurement of cardiac output. Experiments were performed 6-9 days after surgery. Rats were bled to a mean arterial pressure of 40 mmHg and kept at that level using Ringer-lactate solution. Arterial and venous blood pressures, gases, acid-base status, glucose, lactate, electrolytes, hemoglobin, O2 saturation, heart and respiratory rates, total peripheral resistance, and O2 delivery and consumption were measured before hemorrhage, soon after 40 mmHg was reached, and 0.5, 1, 2, 3, and 4 h later. Fifty-three percent of rats survived > or =3 h (survivors); others were considered nonsurvivors. Nonsurvivors showed a significantly greater degree of metabolic acidosis than survivors. Arterial PO2, respiratory rate, O2 saturation, O2 content, glucose, and pH were significantly higher in survivors. The rate of Ringer-lactate infusion, arterial K+, and PCO2 were lower in survivors. Arterial K+ and respiratory rate were the only parameters significantly different between survivors and nonsurvivors at all time points during HH. Arterial levels of K+ showed the clearest distinction between survivors and nonsurvivors and may explain the sudden death experienced by animals during HH. The data suggest that early respiratory and metabolic compensations are essential for survival of prolonged HH.     

Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats

Neuropeptide Y (NPY) is a vasoconstrictor present in the sympatho-adrenomedullary system and may be co-released with norepinephrine (NE) and epinephrine (EPI) during sympathetic activation. We studied plasma NPY-immunoreactivity (-ir, radioimmunoassay) and catecholamine (radioenzymatic) responses during two acute stress paradigms that differ in character, intensity, and duration. The intermittent stress of footshock (0.75 and 1.5 mA, 0.5 sec duration, at 5-sec intervals, for 5 min) evoked intensity-dependent immediate increments in plasma NE and EPI, and a delayed NPY-ir response (+0.6 +/- 0.1 pmol/ml). Prolonged (60 min) immobilization caused greater increases in plasma NE and EPI levels and no changes in plasma NPY-ir until the end of the stress session (+0.3 +/- 0.1 pmol/ml). Plasma NPY-ir responses correlated with those of NE but not with EPI suggesting a sympathetic origin for the release of the peptide. Relatively greater NPY-ir responses to footshock than to immobilization may be consistent with a preferential release of the peptide by a bursting but not continuous mode of sympathetic activation. However, it may also be due to a differential activation of the sympathetic nerves and adrenal medulla by these two stress situations.     

Ketamine inhibits fetal ACTH responses to cerebral hypoperfusion

The present study tested the effect of ketamine on the fetal reflex responses of late-gestation sheep to brachiocephalic occlusion (BCO), a stimulus that mimics the reduction in cerebral blood flow that results from severe fetal hypotension. Ketamine, a dissociative anesthetic and known noncompetitive antagonist of N-methyl D-aspartate (NMDA) receptors, has previously been shown to impair chemoreceptor responsiveness. Studies from this laboratory suggest that fetal reflex ACTH responses to hypotension are largely mediated by chemoreceptors; therefore, we hypothesized that ketamine would inhibit the reflex hormonal response to BCO. Chronically catheterized fetal sheep were subjected to acute cerebral hypoperfusion through occlusion of the brachiocephalic artery. Fetal blood pressure and heart rate were continuously recorded, and fetal blood samples drawn during the experiment were analyzed with specific hormone assays. Our results demonstrate that ketamine attenuates hemodynamic responses to cerebral hypoperfusion and is a potent inhibitor of ACTH and proopiomelanocortin (POMC)/pro-ACTH release. These data support the hypothesis that fetal reflex responses hypotension are chemoreceptor mediated. Given the potency with which ketamine inhibits ACTH response to fetal hypotension, we suggest that the use of ketamine or other anesthetic or analgesic drugs that block or otherwise interact with the NMDA-glutamate pathways, in late pregnancy or in preterm newborns be reconsidered.     

Adrenocortical responses to ACTH (author's transl)]

To characterize by a mathematical model the dynamics of adrenocortical responses to ACTH, the concentration of plasma corticosterone was measured following a series of injections and perfusions of ACTH to dexamethasone-treated male rats. A similar slope was observed during the rise of plasma corticosterone following graded pulse inputs, and the steady-state corticosterone secretion rate was shown to increase proportionally to the perfusion rate of ACTH up to saturation corresponding to maximal secretion. The data will be used, concurrently with our model of the dynamics of plasma cortiscosterone, for the identification of a mathematical model of the adrenocortical response to ACTH.     

Contractile responses of human thyroid arteries to vasopressin

Aims

In the present study we investigated the intervention of nitric oxide and prostacyclin in the responses to vasopressin of isolated thyroid arteries obtained from multi-organ donors.

Main methods

Paired artery rings from glandular branches of the superior thyroid artery, one normal and the other deendothelised, were mounted in organ baths for isometric recording of tension. Concentration–response curves to vasopressin were determined in the absence and in the presence of either the vasopressin V₁ receptor antagonist d(CH₂)₅Tyr(Me)AVP (10^− 8 M), the nitric oxide synthase inhibitor N^G-monomethyl-l-arginine (L-NMMA, 10^− 4 M), or the inhibitor of prostaglandins indomethacin (10^− 6 M).

Key findings

In artery rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions. The vasopressin V₁ receptor antagonist d(CH₂)₅Tyr(Me)AVP (10^− 8 M) displaced the control curve to vasopressin 19-fold to the right in a parallel manner. The contractile response to vasopressin was unaffected by L-NMMA or by indomethacin.

Significance

Vasopressin causes constriction of human thyroid arteries by stimulation of V₁ vasopressin receptors located on smooth muscle cells. These effects are not linked to the presence of an intact endothelium or to the release of nitric oxide or prostaglandins. The constriction of thyroid arteries may be particularly relevant in certain pathophysiological circumstances in which vasopressin is released in amounts that could interfere with the blood supply to the thyroid gland.