Arginine vasopressin (AVP) regulates ACTH release under certain conditions, and exogenously administered AVP is used clinically to stimulate ACTH secretion. We attempted to determine at what plasma concentration AVP can stimulate ACTH release. Six normal men were given infusions of AVP (Ferring) or vehicle between 1600 and 1700 h on five occasions: 1) saline (30 mL/h); 2) 10 ng AVP/min; 3) 30 ng AVP/min; 4) 100 ng AVP/min; and 5) 300 ng AVP/min. Plasma AVP, ACTH, and cortisol concentrations were measured every 10 min during the infusions. Basal plasma AVP levels were less than 1 ng/L (less than 0.92 pmol/L). The lowest AVP dose raised plasma AVP into the range found in fluid-deprived subjects (7-8 ng/L;6.5-7.3 pmol/L), but had no effect on plasma ACTH concentrations. AVP in a dose of 30 ng/min also had no effect. The 100 ng AVP/min dose raised plasma AVP concentrations to 51.4-65.5 ng/L (46-60 pmol/L). This increase led to a transient insignificant increase in plasma ACTH from 13.9 +/- 1.2 (+/- SEM) ng/L (3.1 +/- 0.3 pmol/L) to 20.0 +/- 1.4 ng/L (4.4 +/- 0.3 pmol/L), while plasma cortisol rose significantly from 146 +/- 10 to 209 +/- 19 nmol/L (P less than 0.01) after 60 min of infusion. The 300 ng AVP/min dose raised plasma AVP levels to about 260 ng/L (239 pmol/L); the maximal plasma ACTH and cortisol levels were 39.5 +/- 5.0 ng/L (8.7 +/- 1.1 pmol/L; P less than 0.01) and 348 nmol/L (P less than 0.01), respectively. Thus, peripheral plasma AVP levels have to be raised high above the physiological range before ACTH release is stimulated. We conclude that any AVP reaching the adenohypophysis through the peripheral circulation is of much less importance for the regulation of ACTH secretion than is AVP derived from the pituitary portal circulation.
Experimental evidence indicates that arginine vasopressin contributes to the release of adrenocorticotropic hormone under certain conditions. We studied for the first time the AVP antagonist [d(CH2)5 Tyr(Me)AVP] in 6 normal men in order to evaluate the possible role of AVP as an ACTH-releasing hormone during insulin-induced hypoglycemia. To test the agent's capacity to inhibit an ACTH release by exogenous AVP, we compared the ACTH response to an infusion of 300 ng AVP/min a. 30 min after injection of 5 \g=m\g/kg of the antagonist, b. after injection of placebo (0.9% NaCl). Plasma ACTH levels during AVP infusion rose from 17.2\m=+-\1.6ng/l (3.8\m=+-\0.35 pmol/l) to 31.7\m=+-\4.2ng/l (7.0\m=+-\0.92pmol/l) at 40 min after injection of the antagonist, the difference to the control-group (increment from 16.5\m=+-\1.2 ng/l (3.6\m=+-\0.26pmol/l) to 41.8\m=+-\3.5 ng/l) (9.2\m=+-\0.77pmol/l) being significant (p<0.05). Peak plasma cortisol levels were 323\m=+-\42and 529\m=+-\52nmol/l, respectively (p<0.05). We then tested the compound in the same subjects during an insulin-induced hypoglycemia; 30 min after administration of 10 \g=m\g/kg of the AVP antagonist or placebo, all subjects received 0.12 IU/kg of normal insulin, thus inducing a fall of blood glucose levels below 2 mmol/l. The AVP antagonist caused a moderate but insignificant reduction of the rise in plasma ACTH and a slightly greater, significant reduction of the increment in plasma cortisol (350\m=+-\19 nmol/l with antagonist and 469\m=+-\90nmol/l with placebo, p<0.05) during insulininduced hypoglycemia. The results indicate that a. the AVP antagonist partly inhibits the stimulatory effect of infused AVP on ACTH release in normal men; b. a slightly higher dose of this competitive AVP antagonist inhibits ACTH and cortisol stimulation by hypoglycemia only very little. The importance of AVP as an ACTH\x=req-\ releasing factor in the latter condition may have been underestimated by our experiment, since AVP concentrations in hypophyseal portal blood during hypoglycemia probably were higher than during the AVP infusion experiment.It has been recognized for many years that acute hypoglycemia is a potent stimulus for the release of several anterior pituitary hormones. Hypoglycemia also stimulates the release of arginine vasopressin in humans (1) and rats (2). The physiological re¬ levance of the AVP response to hypoglycemia is unclear. A variety of studies have demonstrated an AVP-induced release of adrenocorticotropic hor¬ mone and a potentiation of the ACTH response to corticotropin-releasing hormone by AVP (3-8), sug¬ gesting that this peptide is involved in ACTH se¬ cretion under certain conditions. Most of the above-mentioned studies attempted to define the role of vasopressin as an ACTH secretagogue by giving it exogenously. Recently, se¬ veral competitive antagonists were synthesized and tested in animals and humans (9-11). The present study was carried out to investigate the role of en¬ dogenous vasopressin in inducing ACTH release during insulin-induced hypo...
Experimental evidence indicates that arginine vasopressin (AVP) contributes to the release of ACTH under certain conditions. The present study investigates the role of vasopressin as a secretagogue of ACTH during cigarette smoking or nicotine infusion with additional injection of corticotropin releasing hormone (CRH) and using the specific AVP antagonist d(CH2)5Tyr(Me)-AVP. We first tested the effect of the AVP antagonist (10 micrograms/kg body weight i.v.) on ACTH and cortisol release following cigarette smoking in 15 healthy young male smokers. Smoking led to marked increments in plasma nicotine and to a small rise in plasma ACTH and cortisol. Mean plasma ACTH and cortisol levels were at no time significantly altered by the antagonist. This might be due to a slight agonistic effect of the AVP antagonist, to high interindividual variability of the ACTH and cortisol responses after smoking or to a negligible role of AVP in smoking-induced ACTH release. In a second study we performed the following tests in six healthy male non-smokers: (1) nicotine infusion (1.0 micrograms/kg body weight per min); (2) CRH i.v. (100 micrograms); (3) AVP antagonist i.v. (5 micrograms/kg); (4) nicotine infusion plus CRH i.v.; (5) nicotine infusion plus AVP antagonist i.v.; (6) nicotine infusion plus CRH and AVP antagonist i.v.; and (7) sham infusion. Nicotine infusion led to greater increments of AVP, ACTH and cortisol than smoking without causing nausea. Peak nicotine levels after nicotine infusion were lower than after smoking. The AVP antagonist in the reduced dosage given alone had no effect on hormone levels. However, it slightly attenuated the effect of nicotine on ACTH and cortisol (P less than 0.05, ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)
Recent data suggest that leukocyte-endothelium activation/interactions are important for restenosis after percutaneous transluminal angioplasty (PTA). Ten patients with superficial femoral artery occlusive disease (stage Fontaine IIb) were examined after a percutaneous transluminal angioplasty (PTA) versus a preceding aortoangiography (AAG). Blood samples from corresponding femoral arteries and veins were obtained before, immediately after, and 4 hours after each procedure. The authors examined the ex vivo respiratory burst and leukocytic expression of adhesion molecules flowcytometrically, adhesion molecule plasma concentrations, and inflammatory mediators concentrations in plasma and in endotoxin-stimulated whole blood cultures by ELISA, and the leukocyte counts. After PTA, venous plasma concentrations of soluble (s)L-selectin (148.2 +/-14.7%, p<0.05 vs 100% baseline +/- sem), sP-selectin (130.7 +/-6.9%, p<0.01; sE-selectin (117.5 +/-8.3%, p<0.05 vs arterial), sLFA-3 (130.7 +/-15.8%, p<0.05) were increased. Expressions of L-selectin (93.0 +/-5.7%, p<0.05 vs arterial), CD11a (98.8 +/-3.8%, p=0.06), CD18 (96.9 +/-4.0%, p<0.05 vs arterial), and ICAM-1 (89.1 +/-7.7%, p<0.05) on polymorphonuclear neutrophils (PMN), and arteriovenous leukocyte counts (arterial: 103.5 +/-5.4%, venous: 91.1 +/-3.3%, p<0.05) decreased. Venous ex vivo secretions of oxygen radicals (141.4 +/-28.1%, p<0.05 vs AAG), PMN-elastase (173.7 +/-35.7%, p<0.05 vs AAG), and interleukin (IL)-8 (226.5 +/-56.4%, p<0.001; p<0.0001 vs AAG), as well as PMN-elastase (173.7 +/-35.7%, p<0.05 vs AAG) and tumor necrosis factor (TNF)-alpha plasma concentrations (124.1 +/-11.9%, p=0.06) rose. Four hours after PTA, a leukocytosis and exhausted TNF-alpha (69.8 +/-10.4%, p<0.05) and IL-8 secretions (72.4 +/-4.6%, p<0.01) occurred. PTA induced local leukocyte-endothelium activations (stronger ex vivo mediator productions) and interactions (decreased venous leukocyte counts, increased plasma concentrations, and decreased leukocytic expression of adhesion molecules) with the release of inflammatory mediators (higher plasma concentrations and exhaustions after 4 hours).
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