Arginine Vasopressin Response Research Articles

Distinct receptor subtypes mediate arginine vasopressin-dependent ACTH release and intracellular calcium mobilization in rat pituitary cells

In the present study, adrenocorticotropic hormone (ACTH) release and intracellular calcium ([Ca2+]i) increase induced by arginine vasopressin (AVP) were characterized in collagenase-dispersed and 3-day cultured rat anterior pituitary cells. AVP and the selective vasopressin V1b receptor agonist, [1-deamino-4-cyclohexylalanine]AVP (d[Cha4]AVP) induced ACTH release with nanomolar potencies in both cell preparations, and produced a maximal stimulation that was about 1.5 fold greater in the 3-day cultured cells, indicating that the vasopressin V1b receptor–ACTH release pathway is enhanced over time in culture. In dispersed cells, AVP, oxytocin and d[Cha4]AVP induced [Ca2+]i increases with nanomolar potencies. The selective vasopressin V1a receptors antagonist, SR49059 (100nM), together with the selective oxytocin receptors antagonist (d(CH2)51Tyr(Me)2,Thr4,Orn8,Tyr-NH29-vasotocin (100nM), inhibited the maximal AVP response by ~70%, without affecting the response to d[Cha4]AVP, suggesting that the V1b receptor was only partially responsible for the AVP-induced [Ca2+]i increase. In contrast, in 3-day cultures, AVP induced an increase in [Ca2+]i, while oxytocin and d[Cha4]AVP did not. The response to AVP was completely antagonized by SR49059, whereas the vasopressin V1b receptor antagonists, SSR149415 and (d(CH2)51Tyr(Me)2,Thr4,Orn8,Tyr-NH29)-vasotocin had no effect, indicating that the [Ca2+]i increase was mediated exclusively by vasopressin V1a receptors. In conclusion, the enhancement of vasopressin V1b receptor-mediated ACTH release and the lack of a detectable vasopressin V1b receptor coupling to [Ca2+]i increase in cultured cells suggests the activation of a different/additional signaling pathway in the molecular mechanism of ACTH release.

Central Diabetes Insipidus and Hypothalamic Type of Hypopituitarism Associated with Atypical Location of Rathke's Cleft Cyst

A 68-year-old woman was admitted to determine the pathogenesis of weight loss and polyuria. Physical findings on admission showed BMI of 20.9, blood pressure of 147/69 mmHg, and that she had ciliac, axillar and pubic hair loss. Laboratory findings showed that plasma adrenocorticotropic hormone (ACTH) was 4.6 pg/mL with serum cortisol of 1.2 µg/dL. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were markedly reduced. Serum growth hormone (GH) and insulin growth factor (IGF)-1 were 0.054 ng/mL and 25 ng/mL, respectively. Serum prolactin was as high as 85.6 ng/mL. The levels of all the pituitary hormones were elevated in response to a mixture of exogenous corticotrophin-releasing hormone (CRH), luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and growth hormone-releasing hormone (GRH). However, there was no response of ACTH and GH release to insulin-induced hypoglycemia and no response of LH and FSH release to clomiphene. Urine volume was more than 4,000 mL, with low urine osmolality of 134 mmol/kg. Plasma arginine vasopressin (AVP) was 0.8 pg/mL. There was no increase in urine osmolality and plasma AVP in response to 5% hypertonic saline load. Magnetic resonance imaging revealed Rathke's cleft cyst at the pituitary stalk level, but there was no abnormal finding in the hypothalamus. These findings indicate central diabetes insipidus and hypothalamic type of hypopituitarism, resulting from the atypical location of Rathke's cleft cyst.

Propranolol modulates the collateral vascular responsiveness to vasopressin via a Gα-mediated pathway in portal hypertensive rats

Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications of portal hypertension and can be controlled with vasoconstrictors. Nevertheless, sympathetic tone abnormality and vascular hyporesponsiveness in portal hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol, a β-blocker binding the G-protein-coupled adrenoceptor, is a portal hypotensive agent. However, whether propranolol influences the collateral vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein ligation) in Sprague-Dawley rats. In an acute study with an in situ perfusion model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated with vehicle, propranolol (10 μmol/l), propranolol plus suramin (100 μmol/l, a G(α) inhibitor) or suramin pre-incubation. G(α) mRNA expression in the splenorenal shunt, the most prominent intra-abdominal collateral vessel, was measured. In the chronic study, rats received DW (distilled water) or propranolol (10 mg x kg(-1) of body weight x day(-1)) for 9 days. Then the concentration-response relationship of AVP and G(α) mRNA expression were assessed. Propranolol pre-incubation elevated the perfusion pressure changes of collaterals in response to AVP, which was inhibited by suramin. The splenorenal shunt G(αq) and G(α11) mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of G(α11) as compared with the propranolol group. Chronic propranolol treatment reduced mean arterial pressure, PP (portal pressure) and the perfusion pressure changes of collaterals to AVP. G(αs) expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to G(αq) and G(α11) up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to G(αs) up-regulation. The G(α) signalling pathway may be a therapeutic target to control variceal bleeding and PP in portal hypertension.

The Science Behind Hyponatremia and Its Clinical Manifestations

Body sodium, water, and extracellular fluid volume are tightly regulated by neural, humoral, and renal mechanisms to maintain osmolality in extracellular fluid and to maintain normal intravascular volume. This is accomplished by controlling sodium content in extracellular fluid. In the normal physiologic state, total body water (which accounts for ~60% of body weight) is distributed among three compartments: intracellular, interstitial, and intravascular spaces. About two thirds of total body water is intracellular fluid. Potassium is the major intracellular cation, and sodium is the major extracellular cation. Body water content and plasma osmolality are tightly regulated by the action of arginine vasopressin on renal tubules. A wide variety of disease states are associated with a nonosmotic response of arginine vasopressin, also known as the antidiuretic hormone. Determination of the serum sodium concentration is the most direct measure of hyponatremia. The vasopressin V(2)-receptor antagonists are effective aquaretic agents and correct hyponatremia in several hyponatremic disorders.

Further studies on the anti-nociceptive effect of vasopressin.

The possible interactions of pathways which mediate anti-nociception when stimulated by alpha 2-adrenoceptor agonists and arginine vasopressin (AVP) were investigated. Yohimbine, an alpha 2-antagonist, failed to modify the anti-nociceptive response of AVP. However, clonidine pretreatment, in sub-effective and effective doses, potentiated the anti-nociceptive response of a sub-effective dose of AVP. This potentiation was attenuated by yohimbine and completely antagonized by naloxone. These studies suggest that pathways related to the opioidergic system and those stimulated by alpha 2-agonists may be utilized by AVP in eliciting the anti-nociceptive response.

Vasopressin-dependent coupling between sodium transport and water flow in a mouse cortical collecting duct cell line

Water balance is achieved through the ability of the kidney to control water reabsorption in the connecting tubule and the collecting duct. In a mouse cortical collecting duct cell line (mCCD(c11)), physiological concentrations of arginine vasopressin increased both electrogenic, amiloride-sensitive, epithelial sodium channel (ENaC)-mediated sodium transport measured by the short-circuit current (Isc) method and water flow (Jv apical to basal) measured by gravimetry with similar activation coefficient K(1/2) (6 and 12 pM, respectively). Jv increased linearly according to the osmotic gradient across the monolayer. A small but highly significant Jv was also measured under isoosmotic conditions. To test the coupling between sodium reabsorption and water flow, mCCD(c11) cells were treated for 24 h under isoosmotic condition with either diluent, amiloride, vasopressin or vasopressin and amiloride. Isc, Jv, and net chemical sodium fluxes were measured across the same monolayers. Around 30% of baseline and 50% of vasopressin-induced water flow is coupled to an amiloride-sensitive, ENaC-mediated, electrogenic sodium transport, whereas the remaining flow is coupled to an amiloride-insensitive, nonelectrogenic sodium transport mediated by an unknown electroneutral transporter. The mCCD(c11) cell line is a first example of a mammalian tight epithelium allowing quantitative study of the coupling between sodium and water transport. Our data are consistent with the 'near isoosmotic' fluid transport model.

Inhibitory Effect of Dexamethasone on Arginine-Vasopressin Release Induced by Physical Exercise in Man

To establish whether glucocorticoids inhibit the arginine-vasopressin (AVP) response to physical exercise, 10 healthy men underwent bicycle ergometer tests until exhaustion (exercise control test, exercise plus dexamethasone [2 or 4...

Increased arginine-vasopressin response to hypertonic stimulation and upright posture in idiopathic hyperprolactinemia

To evaluate the possible influence of idiopathic hyperprolactinemia on the arginine-vasopressin (AVP) response to osmotic and pressure-volumetric stimuli, 14 idiopathic hyperprolactinemic women and 13 normoprolactinemic women were studied during a hypertonic saline infusion test (0.51M NaCl infusion for 2h) and an orthostatic test (standing upright and maintaining an orthostatic position for 20min). In both experimental conditions, the AVP response was significantly higher in women with idiopathic hyperprolactinemia than in normal normoprolactinemic women. These results indicate that in women hyperprolactinemia influences the AVP response to hyperosmotic and hypovolemic stimuli.

Volume regulating hormone responses to repeated head-up tilt and lower body negative pressure

We hypothesized the existence of different hormonal response patterns to repeated lower body negative pressure (LBNP) and head-up tilt (HUT) in healthy males. We compared hormonal, cardiovascular and plasma volume changes from rest to stress within- and between-LBNP and HUT applications. Hormones investigated included adrenocorticotropic hormone (ACTH), aldosterone, plasma renin activity (PRA), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP). Three sequential 30-min bouts of LBNP at -55mmHg (n=14) or 70° HUT (n=9) were preceded by 30-min supine rest, and a 60-min supine rest followed the 3rd stimulus. Plasma renin activity increases above baseline, in relation to aldosterone, were larger with LBNP than with HUT. The 3rd HUT application resulted in a greater increase in aldosterone compared to LBNP. Mean arterial blood pressure was elevated significantly during 1st and 3rd HUT application. ACTH responses were highly correlated with those of aldosterone in both LBNP and HUT (r(2) =0·96). AVP responses, in contrast to ANP, to the three consecutive stress situations were not significantly different, both with LBNP and HUT. We speculate that the observed differences in blood pressure and hormonal responses to LBNP and HUT are caused by divergent effects of blood pooling in the splanchnic region, despite similar reductions in splanchnic perfusion. Apparently with repeated central hypovolaemia, especially by the 3rd application of stress, plasma aldosterone levels rise (along with ACTH), conceivably increasing its volume-guarding effect.

Changes in vasopressin release and autonomic function induced by manipulating forebrain GABAergic signaling under euvolemia and hypovolemia in conscious rats

The anteroventral third ventricular region (AV3V) is a pivotal area for osmotic responses and integration of autonomic functions. The purpose of this study was to investigate whether the gamma-aminobutyric acid (GABA)-ergic activity in the AV3V may be involved in the regulation of arginine vasopressin (AVP) secretion and related phenomena under the conditions with or without hypovolemia. Experiments were performed in conscious rats. We found that AV3V infusion with the GABA(A) receptor antagonist bicuculline in euvolemic rats caused prompt increases in plasma AVP, osmolality, glucose, arterial pressure and heart rate. The effects of the bicuculline infusion were abolished by prior infusion of a GABA(A) receptor agonist, muscimol. When repeated twice with a 10-min interval, removal of systemic blood (10 mL/kg body weight) lowered arterial pressure and enhanced plasma AVP, osmolality, glucose and angiotensin II. Muscimol infusion in the AV3V, but not in the cerebral ventricle, inhibited the responses of plasma AVP and glucose, despite having no effect in a sham hemorrhagic state. The inhibition of the AVP response by the muscimol infusion was also verified in rats given a combined stimulus of bleeding plus an osmotic load. In contrast, AV3V infusion with the GABA(B) receptor agonist baclofen tended to intensify the hemorrhagic responses of plasma AVP and glucose, despite its potency to prevent the hemorrhagic fall in arterial pressure. These results, taken together with our previous data, suggest that hypovolemic stimuli, like hyperosmotic stimuli, may promote AVP secretion by causing the inhibition of AV3V GABA(A)-ergic activity responsible for potentiation of glutamatergic activity.

Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans

We investigated the effect of the intravenous infusion of atrial natriuretic peptide (ANP) on the response of plasma arginine vasopressin (AVP) levels to intravenous infusion of angiotensin II (ANG II) in healthy individuals. Intravenous infusion of ANP (10 ng·kg(-1)·min(-1)) slightly but significantly decreased plasma AVP levels, while intravenous infusion of ANG II (10 ng·kg(-1)·min(-1)) resulted in slightly increased plasma AVP levels. ANG II infused significant elevations in arterial blood pressure and central venous pressure (CVP). Because the elevation in blood pressure could have potentially inhibited AVP secretion via baroreceptor reflexes, the effect of ANG II on blood pressure was attenuated by the simultaneous infusion of nitroprusside. ANG II alone produced a remarkable increase in plasma AVP levels when infused with nitroprusside, whereas the simultaneous ANP intravenous infusion (10 ng·kg(-1)·min(-1)) abolished the increase in plasma AVP levels induced by ANG II when blood pressure elevation was attenuated by nitroprusside. Thus, ANG II increased AVP secretion and ANP inhibited not only basal AVP secretion but also ANG II-stimulated AVP secretion in humans. These findings support the hypothesis that circulating ANP modulates AVP secretion, in part, by antagonizing the action of circulating ANG II.

Simvastatin effects on portal‐systemic collaterals of portal hypertensive rats

Portal-systemic collateral vascular resistance and vasoconstrictor responsiveness are crucial in portal hypertension and variceal bleeding control. Statins enhance vasodilators production, but their influence on collaterals is unknown. This study aimed to survey the effect of simvastatin on collaterals. Partially portal vein-ligated rats received oral simvastatin (20 mg/kg/day) or distilled water from -2 to +7 day of ligation. After hemodynamic measurements on the eighth postoperative day, baseline perfusion pressure (i.e. an index of collateral vascular resistance) and arginine vasopressin (AVP, 0.1 nM-0.1 microM) responsiveness were evaluated with an in situ perfusion model for collateral vascular beds. RT-PCR of endothelial NO synthase (eNOS), inducible NOS (iNOS), cyclooxygenase-1 (COX-1), COX-2, thromboxane A(2) synthase (TXA(2)-S) and prostacyclin synthase genes was performed in parallel groups for splenorenal shunt (SRS), the most prominent intra-abdominal collateral vessel. To determine the acute effects of simvastatin, collateral AVP response was assessed with vehicle or simvastatin. SRS RT-PCR of eNOS, iNOS, COX-1, COX-2 and TXA(2)-S, and measurements of perfusate nitrite/nitrate, 6-keto-PGF1(alpha) and TXB(2) levels were performed in parallel groups without AVP. Acute simvastatin administration enhanced SRS eNOS expression and elevated perfusate nitrite/nitrate and 6-keto-PGF1(alpha) concentrations. Chronic simvastatin treatment reduced baseline collateral vascular resistance and portal pressure and enhanced SRS eNOS, COX-2 and TXA(2)-S mRNA expression. Neither acute nor chronic simvastatin administration influenced collateral AVP responsiveness. Simvastatin reduces portal-systemic collateral vascular resistance and portal pressure in portal hypertensive rats. This may be related to the enhanced portal-systemic collateral vascular NO and prostacyclin activities.

Mechanisms of impaired vasopressin response in acute alcohol‐intoxicated hemorrhaged rats

Acute alcohol intoxication (AAI) blunts the neuroendocrine (catecholamine and arginine vasopressin (AVP)) response to hemorrhagic shock (HS) resulting in impaired blood pressure recovery during fluid resuscitation. Central stimulation of cholinergic nicotinic receptors restores AVP responses in AAI+HS suggesting that AAI disrupts signaling mechanisms controlling AVP release. We hypothesize the AAI‐mediated inhibition of supraoptic (SON) and paraventricular (PVN) responsiveness is controlled by alterations in the balance between inhibitory nitric oxide (NO) and stimulatory angiotensin II (ANG II) signaling. Chronically‐catheterized, adult male Sprague‐Dawley rats (250–300g) received a primed‐constant (2.5g/kg + 0.3g/kg/h) 15h intragastric infusion of alcohol or isocaloric/isovolumic dextrose (DEX). AAI produced a significant (~30%) increase in NO levels in the PVN and SON and NO synthase activity in the SON as compared to DEX controls. AAI did not alter circulating ANG II, but showed significant attenuation of ANG II in response to HS. These results suggest that the mechanisms underlying the attenuation of AVP release during HS in AAI involve altered balance between NO and ANG II control of hypothalamic responses. We predict that central inhibition of NO or ANG II stimulation will restore AVP and will in turn improve hemodynamic recovery from HS in AAI. Supported by DOD PR‐054196 and NIAAA‐AA7577.

Effect of naloxone on the inhibitory effect of melatonin on the release of arginine-vasopressin induced by physical exercise in man

This study was performed in order to establish whether endogenous opioids play a role in the inhibitory effect of melatonin on arginine-vasopressin (AVP) response to physical exercise. Seven healthy men underwent four bicycle ergometer tests until exhaustion [exercise control test, exercise plus naloxone (2 mg injected plus 5 mg infused intravenously), exercise plus melatonin (6 mg), exercise plus melatonin plus naloxone]. Plasma AVP concentrations, non endocrine physiological parameters (NEPP) and biochemical parameters were evaluated during all tests. NEPP and biochemical values had a similar pattern during all tests. Physical exercise significantly increased the AVP levels. The pre-treatment with melatonin inhibited the AVP response to physical exercise. In contrast, naloxone had no effect on AVP rise during exercise, when given alone, whereas it abolished the negative effect of melatonin on AVP response to physical exercise. Our data indicate that naloxone-sensitive endogenous opiates mediate the inhibitory modulation exerted by melatonin on the AVP response to physical exercise.

Sexually diergic, dose-dependent hypothalamic–pituitary–adrenal axis responses to nicotine in a dynamic in vitro perfusion system

Introduction The hypothalamic–pituitary–adrenal cortical (HPA) axis modulates physiological responses to stress. We previously reported sexually diergic, dose-dependent HPA responses in vivo following nicotine administration: Male rats had greater arginine vasopressin (AVP) responses than females, and female rats had greater adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses than males. The goal of the present study was to further investigate sexually diergic, dose-dependent HPA responses following nicotine addition to an in vitro model of the HPA axis, so that hormone output could be determined at each level of the axis. Methods Hypothalami, pituitaries, and adrenal glands were harvested from male and female rats. One-half hypothalamus, one-half pituitary, and one adrenal gland were placed individually into three jacketed tissue baths connected by tubing and perfused in series with physiological medium. Sampling ports between tissue baths were used to collect buffer before and after addition of various doses of nicotine, for measurement of AVP and corticotropin-releasing hormone (CRH) from the hypothalamus bath, ACTH from the pituitary bath, and CORT from the adrenal bath. Hormones were measured by highly specific immunoassays. Results Stable temperatures, flow rates, pH, and hormone baselines were achieved in the in vitro system. Consistent with our in vivo and earlier in vitro studies, nicotine added to the hypothalamus tissue bath significantly increased HPA responses in a sex- and dose-dependent manner: Males had greater AVP responses than did females, and females had greater CRH responses than did males. Sexually diergic ACTH and CORT responses were less apparent and were higher in females. Discussion Our in vitro system accurately models in vivo HPA responses to nicotine in both sexes and thus represents a reliable method for investigating the effects of nicotine on components of the HPA axis. These studies may be pertinent to understanding the biological differences to nicotine between men and women smokers.

Effect of melatonin supplementation on plasma vasopressin response to different conditions in rats with hyperthyroidism induced by l-thyroxine

The present study was performed to determine how basal, isotonic, hypertonic and hypovolemic conditions affect fluid–electrolyte balance and plasma arginine vasopressin (AVP) levels in rats with experimental hyperthyroidism supplemented with melatonin. The rats were divided into four groups of twenty-four subjects each kept under the following treatments during one month: (1) Controls; (2) treated with l-thyroxine; (3) treated with l-thyroxine and sham melatonin and (4) treated with l-thyroxine and melatonin. After this each group was further subdivided into subgroups that were subject to normal, isotonic, hypertonic and hypovolemic conditions. The plasma AVP, total triiodothyronine (TT 3), total thyroxine (TT 4) and melatonin levels were measured in plasma by means of a Phoenix Pharmaceutical RIA test kit. Hematocrit and osmolality levels were also determined. There were significant increases of total T3 and T4 levels in the l-thyroxine treated groups, p < 0.001. The AVP levels were also increased in groups 2 and 3, but not so in the rats treated with melatonin ( p < 0.001), which also showed increased plasma melatonin levels ( p < 0.001). These results indicate that treatment with l-thyroxine increases stimulated and non-stimulated AVP release that are inhibited by melatonin supplementation. It was also shown that AVP response to hypertonic and hypovolemic conditions was not affected by l-thyroxine treatment and/or l-thyroxine + melatonin treatment.

A possible relationship between brain-derived adrenomedullin and oxytocin in the regulation of sodium balance

Exaggerated thirst and salt appetite occurs when endogenous, brain-derived adrenomedullin (AM) production is compromised. In addition, the arginine vasopressin (AVP) response to hypovolemia is compromised. We hypothesized that AM acts in the hypothalamus to control oxytocin (OT) release and that the inhibitory action of AM on salt appetite is mediated via its effects on OT release in the rat. When plasma tonicity was elevated with sodium, ribozyme-induced compromise of central AM production significantly blunted the release of OT into plasma. OT responses to elevation of plasma osmolality without concomitant change in plasma sodium levels were not altered by compromise of AM production. Thus, brain-derived AM controls OT release in response to altered plasma sodium levels. Furthermore, central AM-induced inhibition of NaCl intake can be reversed by pretreatment with an OT antagonist, and the increase in NaCl appetite seen following ribozyme compromise of central AM can be attenuated with central OT administration. These data support the hypothesis that endogenous, brain-derived AM is an essential participant in the hypothalamic response to hypernatremia via its actions on OT-expressing neurons. Together with our previous reports of the effects of AM on AVP secretion and ingestive behaviors, our results suggest that endogenous AM is a physiologically relevant regulator of the endocrine and behavioral mechanisms that maintain fluid and electrolyte homeostasis.

Naloxone decreases the inhibitory effect of ethanol on the release of arginine-vasopressin induced by physical exercise in man

To establish whether ethanol and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, six healthy men underwent six bicycle-ergometer tests until exhaustion [exercise control test; exercise plus ethanol (50 of 110 ml proof whiskey orally), exercise plus naloxone (2 mg injected plus 5 mg infused or 4 mg injected plus 10 mg infused intravenously] or exercise plus ethanol plus naloxone). Plasma AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During the control test, exercise significantly increased plasma AVP levels, with a peak value five times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was abolished by ethanol. When ethanol tests were repeated in the presence of naloxone, at both lower and higher dose, ethanol inhibition on AVP secretion was only partial, with mean peak responses 2.5 times higher than basal values. Results indicate an ethanol involvement in regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying ethanol inhibitory action, but not in mediation of the AVP response to physical exercise.

POSTOPERATIVE VASOPRESSIN AND COPEPTIN LEVELS IN NONCARDIAC SURGERY PATIENTS

Further information on the endogenous arginine vasopressin (AVP) response in patients with postoperative systemic inflammatory response syndrome (SIRS) and vasodilatory shock would provide more insight into the pathophysiology of SIRS-associated cardiovascular failure and help indicate AVP therapy. Patients after uncomplicated abdominal surgery without SIRS (n = 10), critically ill patients after noncardiac surgery with SIRS (n = 9), and patients with SIRS plus vasodilatory shock (n = 22) were included in this prospective trial. Plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations together with clinical parameters were documented daily during the first 7 days postoperative. The AVP response significantly differed between the three groups. Patients without SIRS had lower AVP concentrations than SIRS patients with (P = 0.001) or without shock (P = 0.003). Patients with SIRS and shock had higher AVP levels than patients with SIRS alone (P < 0.001). Arginine vasopressin decreased over time (P = 0.007) in all groups. At day 28, nonsurvivors had higher AVP levels than did survivors (P < 0.001). In SIRS patients without shock, serum osmolarity was indirectly associated with AVP levels, whereas mean arterial blood pressure and serum osmolarity were associated with AVP in SIRS patients with shock. Arginine vasopressin and copeptin correlated significantly with each other (P < 0.001; r = 0.76). In patients without hemofiltration, copeptin levels predicted 28-day mortality with high sensitivity and specificity. The postoperative AVP response in noncardiac surgery patients seems well maintained. The possibility that AVP plays a contributory role in the failure to restore vascular tone in patients with vasodilatory shock cannot be excluded but seems less important than in septic or postcardiotomy shock.

The vasopressin and copeptin response to infection, severe sepsis, and septic shock*

To compare the course of arginine vasopressin (AVP) and copeptin plasma concentrations between patients with infection, severe sepsis, and septic shock. Prospective, closed-cohort study. Twelve-bed general and surgical intensive care unit and 33-bed internal medicine ward in a university hospital. Ten patients with infection, 22 with severe sepsis, and 28 with septic shock. None. Hemodynamic, laboratory and clinical data were recorded daily during the first 7 days after intensive care unit or hospital admission. Parallel thereto, blood was withdrawn to determine plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations. Standard tests, a mixed effects model, and a linear regression analysis were used for statistical analysis. The AVP response was different between the three study groups (p < 0.001) but did not change over time (p = 0.12). Although patients with severe sepsis and septic shock had higher AVP levels than did patients with infection (both p < 0.001), no difference in AVP concentrations was seen between severe sepsis and septic shock patients (p = 0.98). No difference in AVP was observed between survivors and nonsurvivors at day 28 (p = 0.87). In patients with severe sepsis, serum osmolarity (p < 0.001), arterial pH (p = 0.001), lactate (p < 0.001), and Pao2 (p = 0.04) were associated with the course of AVP plasma levels, whereas it was serum osmolarity alone in patients with septic shock (p = 0.03). Plasma AVP concentrations correlated with copeptin (r = .614, p < 0.001), but this correlation was influenced by continuous veno-venous hemofiltration (p = 0.002). Severe sepsis induced a stronger AVP response than infection without systemic inflammation. However, the lack of a difference in AVP plasma concentrations between patients with and without shock indicates that the AVP system does not function normally in severe sepsis. Our data support the hypothesis that impaired AVP response is at least partially responsible for the failure to restore vascular tone in septic shock.