Plasma Vasopressin Levels Research Articles

Antidiuretic Hormone and Osmolality in Patients with Ménière’s Disease

Plasma antidiuretic hormone (p-ADH) and plasma osmolality (p-Osm) levels were studied in patients with Ménière’s disease. In 147 cases, the p-ADH levels were measured during remission and in the acute phase of the disease. In 100 of 147 cases, the p-Osm levels were determined both in remission and in the acute phase. In remission, the p-ADH and p-Osm levels were higher than the normal limits. In the acute phase, the p-ADH level was higher than that in remission, consistent with previous reports. Moreover, the p-Osm level was unchanged. Although the p-ADH level is regulated by that of p-Osm, the kidney must show an escape phenomenon from antidiuresis. Besides, other factors must increase the amount of p-ADH. Further study is needed to reveal the cause of the rise in p-ADH and p-Osm levels.

Blockade of NK3R signaling in the PVN decreases vasopressin and oxytocin release and c-Fos expression in the magnocellular neurons in response to hypotension

Tachykinin neurokinin 3 receptor (NK3R) signaling has a broad role in vasopressin (VP) and oxytocin (OT) release. Hydralazine (HDZ)-induced hypotension activates NK3R expressed by magnocellular neurons, increases plasma VP and OT levels, and induces c-Fos expression in VP and OT neurons. Intraventricular pretreatment with the specific NK3R antagonist, SB-222200, eliminates the HDZ-stimulated VP and OT release. NK3R are distributed in the central pathways conveying hypotension information to the magnocellular neurons, and the NK3R antagonist could act anywhere in the pathways. Alternatively, the antagonist could act at the NK3R expressed by the magnocellular neurons. To determine whether blockade of NK3R on magnocellular neurons impairs VP and OT release to HDZ, rats were pretreated with a unilateral PVN injection of 0.15 M NaCl or SB-222200 prior to an intravenous injection of 0.15 M NaCl or HDZ. Blood samples were taken, and brains were processed for VP/c-Fos and OT/c-Fos immunohistochemistry. Intravenous injection of 0.15 M NaCl did not alter plasma hormone levels, and little c-Fos immunoreactivity was present in the PVN. Conversely, intravenous injection of HDZ increased plasma VP and OT levels and c-Fos expression in VP and OT magnocellular neurons. Intra-PVN injection of SB-222200 prior to an intravenous injection of HDZ significantly decreased c-Fos expression in both VP and OT neurons by approximately 70% and attenuated plasma VP and OT levels by 33% and 35%, respectively. Therefore, NK3R signaling in magnocellular neurons has a critical role for the release of VP and OT in response to hypotension.

Melatonin and the Synthesis of Vasopressin in Pinealectomized Male Rats

Abstract. The pineal hormone, melatonin, is known to modify, under different experimental conditions, neurohypophysial hormone secretion in the rat. The aim of this study was to investigate the effect of melatonin on the vasopressin biosynthesis rate in the hypothalamus of either pinealectomized or sham-operated rats, using the colchicine method. To estimate whether colchicine affects the function of the neurohypophysis in these animals, the neurohypophysial and plasma vasopressin levels were also measured.The vasopressin synthesis rate was increased after pineal removal, when compared with sham-operated animals, and melatonin strongly inhibited the rise in the hormone synthesis due to pinealectomy. After pineal removal plasma vasopressin concentration was significantly elevated, and melatonin attenuated this effect. On the contrary, the neurohypophysial vasopressin content was significantly decreased after pinealectomy, but it was not further modified by melatonin.Thus, melatonin suppresses the synthesis and secretion of vasopressin in pinealectomized rats. The present results confirm our previous reports as to the inhibitory impact of the pineal on both vasopressin synthesis and release and suggest that melatonin may mediate the effect of the pineal gland on vasopressinergic neuron activity.

Ethnic Differences in Renal Responses to Furosemide

Blacks have a greater tendency to retain Na than whites. The present study sought evidence for ethnic differences in parameters reflective of Na uptake by the Na,K,2Cl cotransporter in the thick ascending limb, namely, the urine concentration and urinary excretion of certain cations before and after furosemide administration (40 mg IV). Subjects were healthy (ages 18 to 36 years). During the preceding overnight period, urine volume was lower, and osmolality was higher in blacks than in whites, an ethnic difference that disappeared when water intake was restricted to infused normal saline (60 mL/h). Plasma vasopressin levels were higher in black males than in other sex/ethnic groups. Baseline urinary excretion rates of K, Ca, and Mg were significantly lower in blacks than in whites. After furosemide (0 to 1 hour), K and Ca excretion rates increased, but the proportionate ethnic difference decreased from 44% to 22% and from 22% to 10%, respectively, consistent with blacks having more basal Na,K,2Cl cotransporter activity to inhibit. During a later postfurosemide period (1 to 5 hours), urinary concentrations of Ca and Mg recovered more slowly in blacks, consistent with greater reuptake in the thick ascending limb. In summary, there were distinct ethnic differences in renal handling of Ca and Mg basally and in response to furosemide that were consistent with a more active Na,K,2Cl cotransporter in the thick ascending limb in blacks. An increase in vasopressin levels appeared to explain greater urine concentrations in black males but not black females.

Sodium Excretion in Response to Vasopressin and Selective Vasopressin Receptor Antagonists

The mechanisms by which arginine vasopressin (AVP) exerts its antidiuretic and pressor effects, via activation of V2 and V1a receptors, respectively, are relatively well understood, but the possible associated effects on sodium handling are a matter of controversy. In this study, normal conscious Wistar rats were acutely administered various doses of AVP, dDAVP (V2 agonist), furosemide, or the following selective non-peptide receptor antagonists SR121463A (V2 antagonist) or SR49059 (V1a antagonist). Urine flow and sodium excretion rates in the next 6 h were compared with basal values obtained on the previous day, after vehicle treatment, using each rat as its own control. The rate of sodium excretion decreased with V2 agonism and increased with V2 antagonism in a dose-dependent manner. However,for comparable increases in urine flow rate, the V2 antagonist induced a natriuresis 7-fold smaller than did furosemide. Vasopressin reduced sodium excretion at 1 mug/kg but increased it at doses >5 umg/kg,an effect that was abolished by the V1a antagonist. Combined V2 and V1a effects of endogenous vasopressin can be predicted to vary largely according to the respective levels of vasopressin in plasma,renal medulla (acting on interstitial cells), and urine (acting on V1a luminal receptors). In the usual range of regulation, antidiuretic effects of vasopressin may be associated with variable sodium retention. Although V2 antagonists are predominantly aquaretic, their possible effects on sodium excretion should not be neglected. In view of their proposed use in several human disorders, the respective influence of selective (V2) or mixed (V1a/V2) receptor antagonists on sodium handling in humans needs reevaluation.

Peripheral mechanisms involved in the pressor and bradycardic effects of centrally administered arachidonic acid

In the current study, we aimed to determine the cardiovascular effects of arachidonic acid and peripheral mechanisms mediated these effects in normotensive conscious rats. Studies were performed in male Sprague Dawley rats. Arachidonic acid was injected intracerebroventricularly (i.c.v.) at the doses of 75, 150 or 300 μg and it caused dose- and time-dependent increase in mean arterial pressure and decrease in heart rate in normal conditions. Maximal effects were observed 10 min after 150 and 300 μg dose of arachidonic acid and lasted within 30 min. In order to evaluate the role of main peripheral hormonal mechanisms in those cardiovascular effects, plasma adrenaline, noradrenaline, vasopressin levels and renin activity were measured after arachidonic acid (150 μg; i.c.v.) injection. Centrally injected arachidonic acid increased plasma levels of all these hormones and renin activity. Intravenous pretreatments with prazosin (0.5 mg/kg), an α 1 adrenoceptor antagonist, [ β-mercapto- β, β-cyclopentamethylenepropionyl 1, O-Me-Tyr 2-Arg 8]-vasopressin (10 μg/kg), a vasopressin V 1 receptor antagonist, or saralasin (250 μg/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to arachidonic acid (150 μg; i.c.v.) while combined administration of these three antagonists completely abolished the effect. Moreover, both individual and combined antagonist pretreatments fully blocked the bradycardic effect of arachidonic acid. In conclusion, our findings show that centrally administered arachidonic acid increases mean arterial pressure and decreases heart rate in normotensive conscious rats and the increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity appear to mediate the cardiovascular effects of the drug.

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin 2 in Experimental Heart Failure

Adrenomedullin 2 (AM2) is a novel member of the calcitonin gene-related peptide family that is thought to play a regulatory role in circulatory homeostasis under normal physiological conditions. The effects of AM2 in heart failure have not been investigated previously. Two incremental doses of human AM2 (10 and 100 ng[kg.min] for 90 minutes each) were given by intravenous infusion to 8 sheep with pacing-induced heart failure. Compared with time-matched control infusions, AM2 produced dose-dependent increases in left ventricular dP/dt(max) (control 1168+/-138 mm Hg/s versus AM2 high-dose 1402+/-130 mm Hg/s; P<0.01) and cardiac output (2.09+/-0.66 L/min versus 3.81+/-0.30 L/min; P<0.001) and reductions in calculated total peripheral resistance (40+/-6 mm Hg(L.min) versus 21+/-4 mm Hg(L.min); P<0.001), mean arterial pressure (74.4+/-2.4 mm Hg versus 66.2+/-2.5 mm Hg; P<0.001), and left atrial pressure (23.3+/-1.0 mm Hg versus 18.8+/-1.3 mm Hg; P<0.001). AM2 administration also induced significant elevations in plasma cAMP (P<0.01) in association with rises in atrial (P<0.05) and brain (P<0.01) natriuretic peptides and plasma renin activity (P<0.01). Despite the increase in renin activity, plasma aldosterone levels were not significantly altered, whereas the aldosterone/plasma renin activity ratio was reduced (P=0.08). Plasma vasopressin, endothelin-1, and catecholamines levels were also unchanged by AM2. Renal effects of AM2 included increased excretion of sodium (P<0.05), cAMP (P<0.01), and creatinine (P<0.05), with augmented creatinine clearance (P<0.05), and a trend for urine output to rise (P=0.068). These results indicate that AM2 administration has favorable effects on cardiovascular, endocrine, and renal indexes in heart failure and identify the peptide as a potential therapeutic target in this disease.

Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes

BackgroundCongenital nephrogenic diabetes insipidus (NDI) is characterised by an inability to concentrate urine despite normal or elevated plasma levels of the antidiuretic hormone arginine vasopressin. We report a Japanese extended family with NDI caused by an 11.2-kb deletion that includes the entire AVPR2 locus and approximately half of the Rho GTPase-activating protein 4 (ARHGAP4) locus. ARHGAP4 belongs to the RhoGAP family, Rho GTPases are critical regulators of many cellular activities, such as motility and proliferation which enhances intrinsic GTPase activity.ARHGAP4 is expressed at high levels in hematopoietic cells, and it has been reported that an NDI patient lacking AVPR2 and all of ARHGAP4 showed immunodeficiency characterised by a marked reduction in the number of circulating CD3+ cells and almost complete absence of CD8+ cells.MethodsPCR and sequencing were performed to identify the deleted region in the Japanese NDI patients. Immunological profiles of the NDI patients were analysed by flow cytometry. We also investigated the gene expression profiles of peripheral blood mononuclear cells (PBMC) from NDI patients and healthy controls in microarray technique.ResultsWe evaluated subjects (one child and two adults) with 11.2-kb deletion that includes the entire AVPR2 locus and approximately half of the ARHGAP4. Hematologic tests showed a reduction of CD4+ cells in one adult patient, a reduction in CD8+ cells in the paediatric patient, and a slight reduction in the serum IgG levels in the adult patients, but none of them showed susceptibility to infection. Gene expression profiling of PBMC lacking ARHGAP4 revealed that expression of RhoGAP family genes was not influenced greatly by the lack of ARHGAP4.ConclusionThese results suggest that loss of ARHGAP4 expression is not compensated for by other family members. ARHGAP4 may play some role in lymphocyte differentiation but partial loss of ARHGAP4 does not result in clinical immunodeficiency.

Tachykinin neurokinin 3 receptor signaling in cholecystokinin-elicited release of oxytocin and vasopressin

Neurokinin 3 receptor (NK3R) signaling has an integral role in the stimulated oxytocin (OT) and vasopressin (VP) release in response to hyperosmolarity and hypotension. Peripheral injections of cholecystokinin (CCK) receptor agonists for the CCK-A (sulfated CCK-8) and CCK-B (nonsulfated CCK-8) receptors elicit an OT release in rat. It is unknown whether NK3R contributes to this endocrine response. Freely behaving male rats were administered an intraventricular pretreatment of 250 or 500 pmol of SB-222200, a specific NK3R antagonist, or 0.15 M NaCl before an intraperitoneal or intravenous injection of CCK-8 (nonsulfated or sulfated) or 0.15 M NaCl. Blood samples were taken before intraventricular treatment and 15 min after intraperitoneal or intravenous injection, and plasma samples were assayed for OT and VP concentration. Intraperitoneal injection of both nonsulfated and sulfated CCK-8 significantly increased plasma OT levels and had no effect on plasma VP levels. Intravenous injection of sulfated CCK-8 stimulated an increase in plasma OT levels and did not alter plasma VP levels. However, intravenous injection of nonsulfated CCK-8 stimulated a significant increase in plasma levels of both OT and VP. No other studies have demonstrated CCK-8-stimulated release of VP in rat. NK3R antagonist did not alter baseline levels of either hormone. However, pretreatment of NK3R antagonist significantly blocked the CCK-stimulated release of OT in all CCK treatment groups and blocked VP release in response to intravenous injection of nonsulfated CCK-8. Therefore, central NK3R signaling is required for OT and VP release in response to CCK administration.

Insufficient Vasopressin Release From Adequate Pituitary Stores Contributes to Inappropriately Low Plasma Vasopressin Levels in the Acute Response to Septic Shock

Inadequate endogenous vasopressin (eVP) levels have been well described in catecholamine resistant hypotension in the setting of septic shock. In a piglet model of endotoxin (ETX) induced septic shock, we examined possible mechanisms for why eVP may not achieve adequate levels to reverse hypotension. eVP response to a 37% decrease in mean arterial pressure achieved levels of 150 ± 10 pg/mL (n=45) which were not sufficient to raise blood pressure. Plasma VP (pVP) levels achieved with pharmacologically administered vasopressin (VP) at 1, 10, and 100 ng/kg/min revealed that pVP levels of at least 400 pg/mL were needed to reverse hypotension (p&lt;0.05). For piglets given ETX, pituitary levels of VP were measured and found to still contain adequate stores (735 ± 51 ng/pit) although decreased from non‐ETX controls (1297 ± 290 ng/pit) . Next we examined whether eVP could be further released by other stimuli in the face of endotoxic hypotension. Dopamine was infused in piglets who had the same degree of hypotension as untreated controls and was found to further increase pVP to 203.5 pg/mL ± 34.5, p&lt;0.02. Given these results it appears that the pituitary has the stores and the capacity to release more eVP in septic shock. The mechanism responsible for low levels of pVP therefore seems to be due at least in part to the inability of the pituitary to adequately release the hormone in response to endotoxin‐induced hypotension.

Inhibitory effect of vasopressin receptor antagonist OPC-31260 on experimental brain oedema induced by global cerebral ischaemia

The effects of the non-peptide vasopressin V(2) receptor antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6 h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration. Electron microscopic examinations revealed typical ischaemic changes after the carotid ligation. The carotid ligation increased the brain contents of water and Na(+) and enhanced the plasma vasopressin level. The increased brain water and Na(+) accumulation was prevented by OPC-31260 administration, but the plasma vasopressin level was further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of the disturbances in brain water and electrolyte balance in response to general cerebral hypoxia. The carotid ligation-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on the renal vasopressin V(2) receptors. These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.

The Management of Ascites and Hyponatremia in Cirrhosis

Ascites is the most common complication of cirrhosis and is associated with an increased risk for the development of infections, dilutional hyponatremia, renal failure, and mortality. Cirrhotic patients who develop ascites and associated complications have a low probability of long-term survival without liver transplantation, and therefore should be referred for evaluation of liver transplantation. While the initial management of uncomplicated ascites with low-sodium diet and diuretic treatment is straightforward in the majority of patients, there is a group of patients who fail to respond to diuretics and develop refractory ascites. The development of specific associated complications such as dilutional hyponatremia may further challenge the management of patients with ascites. New pharmacological agents such as the V2 receptor antagonists, drugs that directly antagonize the effects of elevated plasma antidiuretic hormone levels, induce solute-free water diuresis and seem to be promising in the management of patients with cirrhosis, ascites, and dilutional hyponatremia. This article focuses on the pathophysiology, clinical consequences, current management, and new treatment modalities for ascites and dilutional hyponatremia in cirrhosis.

Stress Hormone Responses During 24-Hour Hypoxemia in Preterm Goat Fetus

Fetal endocrinological responses to chronic hypoxemia are useful in elucidating the process of growth restriction at earlier stages of fetal development. The purpose of this study was to observe endocrinological responses to prolonged (24-h) non-acidemic hypoxemia in preterm goat fetuses. Fetal hormonal changes were examined in chronically instrumented goat fetuses at gestational day 96-102 (0.7 gestation) during continuous nitrogen infusion into the maternal trachea to create prolonged fetal hypoxemia. Plasma levels of arginine vasopressin (AVP), epinephrine, norepinephrine, adrenocorticotropic hormone (ACTH) and cortisol were measured, along with fetal heart rate (FHR) and fetal blood pressure (FBP). Fetal arterial pO(2) declined significantly from 25.0 +/- 1.0 mmHg at baseline to 15.3 +/- 1.0 mmHg after 2 h of hypoxemia, then remained at this level. FHR increased significantly throughout the experiment, but FBP remained unchanged. AVP and ACTH levels rose significantly after 2 h of hypoxemia, and declined to the control values after 12 h. There was no significant increase in the epinephrine level during 24-hr hypoxemia. In contrast, norepinephrine significantly increased after 2 h of hypoxemia and remained at the elevated levels throughout the remainder of the experiment. Thus, preterm fetuses could respond to acute hypoxic stress by increasing the plasma levels of AVP, norepinephrine and ACTH. However, despite the rapid increase in ACTH, the level of cortisol in the fetal plasma was significantly elevated only after 18 h of hypoxemia. The chemoreceptors of preterm fetuses, which regulate the release of cortisol or epinephrine, may be less sensitive to hypoxic insults.

Differential Kinetics of Oxytocin and Vasopressin Heteronuclear RNA Expression in the Rat Supraoptic Nucleus in Response to Chronic Salt Loading In vivo

Previous studies have shown that the secretion of oxytocin and vasopressin from the posterior pituitary always accompanies systemic hyperosmotic stimuli in rats, and that oxytocin and vasopressin mRNAs consistently increase in response to prolonged hyperosmotic stimuli. Hence, it has been widely interpreted that oxytocin and vasopressin secretion and gene expression are closely coupled. In the present study, we used both vasopressin and oxytocin intron- specific probes to measure vasopressin and oxytocin heteronuclear RNA (hnRNA) levels, respectively, by in situ hybridisation in the rat supraoptic nucleus (SON) in conjunction with radioimmunoassays of vasopressin and oxytocin peptide levels in plasma and in the posterior pituitary in normally hydrated rats and after 1-5 days of salt loading. Increased oxytocin secretion in response to hyperosmotic stimuli exceeded vasopressin secretion at every time point studied. Vasopressin hnRNA in the SON increased to near maximal levels within minutes after the hyperosmotic stimulus, and was maintained throughout all 5 days of salt loading. By contrast, oxytocin hnRNA did not significantly change from control levels until approximately 2 days after hyperosmotic stimulation, and was not maximal until 3 days. In summary, increases in oxytocin gene transcription in response to osmotic stimuli are dramatically delayed compared to increases in vasopressin gene transcription under the same conditions. These data indicate that oxytocin gene transcription is not as closely correlated with pituitary peptide secretion as is vasopressin gene transcription, and suggests that there is a fundamental difference in excitation-secretion-transcription coupling mechanisms that regulate these two closely related genes in the rat magnocellular neurones in the SON.

Autonomic dysfunction in experimental sepsis induced by cecal ligation and puncture

A systemic inflammatory response to infection characterizes sepsis which associated to refractory hypotension, turns into severe sepsis. Our aim was to evaluate hormonal and cardiovascular alterations after experimental sepsis induced by cecal ligation and puncture (CLP). Male Wistar rats (200–250 g) were submitted to CLP or sham operation. The animals were decapitated at 0, 2, 4, 6 and 8 h after surgery for collection of blood samples for plasma osmolality, sodium and vasopressin (AVP) measurements. The mean arterial pressure (MAP) and heart rate (HR) were recorded 1 h before and to each 1 h during 5hs after surgery. The spontaneous baroreflex sensitivity and spectral analysis of HR and MAP variability were analyzed after recording. The plasma osmolality and sodium did not show any alterations compared to the sham group. MAP decreased from 3 h (85 vs.103 mm Hg, P < 0.05) to 5 h in the CLP group (76 vs.106 mm Hg, P < 0.05). This was accompanied by an increase in HR. The AVP plasma level was elevated at 4 h (6.0 ± 1.1 vs. 1.1 ± 0.2 pg/mL, P < 0.05) and returned to basal levels at 8 h after CLP (2.3 ± 0.5 vs. 1.9 ± 0.2 pg/mL, P > 0.05). A reduction in baroreflex sensitivity occurred 1 h after injury. The CLP group showed a reduction in overall variability, low-frequency power, and low/high-frequency ratio of HR and low-frequency power of MAP. The data suggest an impairment of autonomic control of the heart and vessels during polymicrobial sepsis. This reduction in autonomic nervous system activity causes the impairment of baroreflex that in turn may contribute to the reduction of vasopressin plasma levels in the late phase of severe sepsis.

Cardiovascular effects of centrally injected melittin in hemorrhaged hypotensive rats: The investigation of peripheral mechanisms

We have previously shown that centrally injected melittin, a phospholipase A(2) (PLA(2)) activator, increases blood pressure and decreases heart rate in the normotensive conscious rats. In the current study we aimed to determine the cardiovascular effects of melittin in hemorrhaged hypotensive rats and to investigate the mediation of peripheral adrenergic, vasopressinergic and renin angiotensin system in the pressor effect of centrally administrated melittin in both normotensive and hypotensive conditions. Acute hypotensive hemorrhage was performed by withdrawing a total volume of 2.2ml of blood/100g body weight over a period of 10min. Melittin was injected intracerebroventricularly (i.c.v.) at the doses of 1.5microg, 3.0microg or 6.0microg after the stabilization period of hemorrhage procedure. We also repeated previous experiments by injecting melittin (1.5microg, 3.0microg or 6.0microg; i.c.v.) to the normotensive animals. Melittin caused dose- and time-dependent increases in mean arterial pressure (MAP) in normal and hypotensive conditions and decreases in heart rate (HR) in normotensive conscious animals. In hypotensive rats, melittin injected at the dose of 6.0microg completely restored the decrease in blood pressure. Plasma adrenaline, noradrenaline, vasopressin levels and renin activity increased after melittin (3.0microg; i.c.v) administration in normal conditions. Hemorrhage, itself, produced an increase in these plasma hormone levels and melittin (3.0microg; i.c.v.) caused additional increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity in hypotensive conditions. Intravenous pretreatments of rats with prazosin (0.5mg/kg), an alpha(1) adrenoceptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Me-Tyr(2)-Arg(8)]-vasopressin (10microg/kg), a vasopressin V(1) receptor antagonist, or saralasin (250microg/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to melittin (3.0microg; i.c.v.) in both normotensive and hypotensive conditions. Besides, the combined administration of these three antagonists before melittin completely abolished the pressor responses to drug in both conditions. Results show that centrally administered melittin, a PLA(2) activator, increases blood pressure and reverses hypotension in hemorrhagic shock. The increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity mediate the pressor responses to melittin in normal and hypotensive conditions.

Conivaptan: A Dual Receptor Vasopressin V1a/V2 Antagonist

Several fluid retentive states such as heart failure, cirrhosis of the liver, and syndrome of inappropriate antidiuretic hormone secretion are associated with inappropriate elevation in plasma levels of arginine vasopressin (AVP), a neuropeptide that is secreted by the hypothalamus and plays a critical role in the regulation of serum osmolality and in circulatory homeostasis. The actions of AVP are mediated by three receptor subtypes V1a, V2, and V1b. The V1a receptor regulates vasodilation and cellular hypertrophy while the V2 receptor regulates free water excretion. The V1b receptor regulates adrenocorticotropin hormone release. Conivaptan is a nonpeptide dual V1a/V2 AVP receptor antagonist. It binds with high affinity, competitively, and reversibly to the V1a/V2 receptor subtypes; its antagonistic effect is concentration dependent. It inhibits CYP3A4 liver enzyme and elevates plasma levels of other drugs metabolized by this enzyme. It is approved only for short-term intravenous use. Infusion site reaction is the most common reason for discontinuation of the drug. In animals conivaptan increased urine volume and free water clearance. In heart failure models it improved hemodynamic parameters and free water excretion. Conivaptan has been shown to correct hyponatremia in euvolemic or hypervolemic patients. Its efficacy and safety for short-term use have led to the Food and Drug Administration (FDA) approval of its intravenous form for the correction of hyponatremia in euvolemic and hypervolemic states. Despite its ability to block the action of AVP on V1a receptors, no demonstrable benefit from this action was noted in patients with chronic compensated heart failure and it is not approved for this indication. Consideration should be given to further evaluation of its potential benefits in patients with acute decompensated heart failure.

Hyponatremic seizure associated with acute respiratory infection

A 66-year-old woman was admitted to our hospital because of vomiting and appetite loss. For the 2 days prior to admission, she had a cold, which had developed into acute viral bronchitis on admission. Because laboratory data on admission showed hyponatremia, intravenous infusion of Ringer's lactate solution was started. However, generalized seizures appeared, and she developed a coma on the day of admission. Her plasma antidiuretic hormone (ADH) level was high in the context of a low serum osmolality on the second hospital day. The infusion rate was increased, and the patient's consciousness level returned to normal. However, her normalized serum Na level declined again as she drank much water to reduce throat discomfort. As the throat discomfort caused by the throat inflammation improved with azulene gargling, her water intake was reduced, and the serum Na concentration returned to normal. Thus, polydipsia caused by a throat inflammation partially contributed to hyponatremia in this patient. We note that increased ADH secretion has been reported in adults with acute respiratory infection. Therefore, we concluded that polydipsia caused by the throat inflammation, plus increased ADH secretion, resulted in hyponatremia in this patient. We should pay attention to the behavior of drinking extra fluid in patients with acute respiratory infections.

The Relevance of an Elevation in the Plasma Vasopressin Levels to the Pathogenesis of Meniere's Attack

An elevation of plasma vasopressin levels has been frequently observed in Meniere's disease patients. However, little is known regarding the mechanism behind this elevation. The plasma vasopressin levels and plasma osmolality were therefore determined in 18 diagnosed Meniere's disease patients and 20 patients with other types of vertigo, who required admission for severe vertigo attacks. All participants were given questionnaires regarding their clinical and psychological status, including their stress levels and depression status, to evaluate environmental stress events. The plasma vasopressin levels of Meniere's disease patients in the acute phase (4.1 +/- 1.37 pg/ml) were significantly higher compared with with those of other vertigo patients in the acute phase (2.1 +/- 0.41 pg/ml) (P < 0.01). The average plasma osmolality of the Meniere's disease group was higher than that of the other vertigo patients group (P < 0.05). No significant difference in reported stress levels, depression status and prevalence of primary headache between the groups was observed. The plasma vasopressin showed no significant correlation with the patients' clinical data (occurrence of emesis or nausea, prevalence of primary headache, depression status and stress). No correlation between the plasma vasopressin and the plasma osmolarity was observed in the Meniere's disease group. These results suggest that the elevation of plasma vasopressin in the acute phase of Meniere's disease is therefore related to the pathogenesis of Meniere's attacks, and the results obtained may provide helpful information for distinguishing between Meniere's disease and other various inner ear diseases.

Sertraline, a selective serotonin reuptake inhibitor, affects thirst, salt appetite and plasma levels of oxytocin and vasopressin in rats

We investigated the effects of chronic administration of sertraline (SERT; approximately 20 mg kg(-1) day(-1) in drinking water), a selective serotonin reuptake inhibitor, on water and sodium intake and on plasma levels of oxytocin (OT) and vasopressin (AVP) in basal and stimulated conditions. Basal water intake was reduced in SERT-treated rats. After 24 h of water deprivation, rats treated with SERT for 21 days ingested less water than the control rats (9.7 +/- 0.5 versus 20.0 +/- 0.9 ml, respectively, at 300 min after water presentation, P < 0.0001). Subcutaneous injection of 2 m NaCl or isoproterenol evoked a lower dipsogenic response in rats treated with SERT for 21 days. Fluid and food deprivation also induced a weaker dipsogenic response in SERT-treated rats (1.6 +/- 0.5 versus 10.2 +/- 1.2 ml, at 300 min, P < 0.0001) but had no effect on saline intake. Sodium depletion induced a higher natriorexigenic response in the SERT group (5.6 +/- 1.3 versus 1.2 +/- 0.3 ml, at 300 min, P < 0.0002). Higher urinary density and lower plasma sodium levels were observed after SERT treatment. Sertraline also increased plasma levels of vasopressin and oxytocin (AVP, 2.65 +/- 0.36 versus 1.31 +/- 0.16 pg ml(-1), P < 0.005; OT, 17.16 +/- 1.06 versus 11.3 +/- 1.03 pg ml(-1), P < 0.0009, at the third week post-treatment). These data constitute the first evidence that chronic SERT treatment affects water and sodium intake in rats. These effects seem to be related to the hyponatraemia caused by the higher plasma levels of AVP and OT.