Plasma Vasopressin Research Articles

Oxytocin and Vasopressin Levels and Related Factors in Adolescents with Social Phobia and Other Anxiety Disorders

ObjectiveThis study aimed to determine whether a difference exists in plasma oxytocin and vasopressin levels among social anxiety disorder, other anxiety disorders, and healthy control groups in adolescents. The relationship between several psychiatric variables (i.e., state and trait anxiety, social anxiety, childhood trauma, and behavioral inhibition) and oxytocin or vasopressin levels were also investigated in adolescents with anxiety disorders.MethodsThe study included three groups of adolescents social anxiety disorder (n = 29), those with other anxiety disorders (n = 27), and the control group (n = 28). The participants filled out self-report scales to determine various psychological variables. Oxytocin and vasopressin levels were determined from the blood samples of the participants.ResultsThe oxytocin levels did not show a significant difference between the social anxiety disorder group and the other anxiety disorders group. However, the oxytocin levels were significantly higher in the social anxiety disorder and other anxiety disorders groups than in the control group. The vasopressin levels did not show a significant difference among the groups. According to the hierarchical regression analysis, the state and trait anxiety levels predicted oxytocin in opposite directions. Oxytocin showed positive and negative relationship with trait and state anxiety respectively. No predictive factors were found for the vasopressin levels.ConclusionWe found that the oxytocin levels of adolescents with social anxiety disorder were not different from those of adolescents with other anxiety disorders. Further studies can improve our knowledge of the relationship among anxiety disorders and oxytocin or vasopressin.

Chronic Lithium Therapy and Urine-Concentrating Ability in Individuals With Bipolar Disorder: Association Between Daily Dose and Resistance to Vasopressin and Polyuria

IntroductionLithium treatment can induce nephrogenic diabetes insipidus (NDI), but no consensus intervention is offered to date. We evaluated in these patients patterns of urine concentration and the correlates of 24-hour urine output.MethodsProspective, single-center, observational study of 217 consecutive lithium-treated individuals, with 24-hour urine collection, desmopressin (1-deamino-arginine vasopressin [DDAVP]) concentrating test, fasting plasma vasopressin measurement (copeptin measurement in n = 119), and measured glomerular filtration rate (mGFR). Maximal urine osmolality (MaxUosm) was the highest level during the DDAVP test.ResultsOf the individuals, 21% displayed polyuria (>3 l/d), but 55% displayed elevated fasting vasopressin level (>5 pg/ml). Uosm was significantly lower and urinary output and free water clearance were significantly higher in individuals treated for >10 years. MaxUosm was >600 mOsm/KgH2O in 128 patients (59%), among which vasopressin was increased in 51%, associated with higher lithium dose (950 [750–1200] vs. 800 [500–1000] mg/d, P < 0.001). All patients with lithium daily dose ≥1400 mg/d had high vasopressin levels. In multivariable analysis, 24-hour urine output was associated with higher lithium daily dose (β 0.49 ± 0.17, P = 0.005), female sex (β −359 ± 123, P = 0.004), daily osmolar intake (β 2.21 ± 0.24, P < 0.001), MaxUosm (β −2.89 ± 0.35, P < 0.001), and plasma vasopressin level (β 10.17 ± 4.76, P = 0.03).ConclusionHigher lithium daily dose was associated with higher vasopressin levels and higher urine output, independently of other factors. Daily osmolar intake was also associated with higher 24-hour urine output. These results suggest that controlled salt and protein intake and lithium dose might reduce polyuria in these patients.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

A Novel Form of Familial Vasopressin Deficient Diabetes Insipidus Transmitted in an X-linked Recessive Manner.

Familial pituitary diabetes insipidus has been described only in an autosomal dominant or recessive mode of inheritance. This work aims to determine the cause of a novel form of familial diabetes insipidus (DI) that is controlled by desmopressin therapy but segregates in an X-linked recessive manner. Thirteen members from 3 generations of the kindred with familial DI were studied. Water intake, urine volume, urine osmolality, plasma osmolality, and plasma vasopressin were measured under basal conditions, during fluid deprivation, 3% saline infusion, and water loading. Magnetic resonance images of the posterior pituitary also were obtained. In affected males, the effects of desmopressin therapy and linkage of the DI to markers for chromosome Xq28 were determined. In addition, the genes encoding vasopressin, aquaporin-2, the AVPR2 receptor, and its flanking regions were sequenced. This study showed that 4 males from 3 generations of the kindred have DI that is due to a deficiency of vasopressin, is corrected by standard doses of desmopressin, and segregates with markers for the AVPR2 gene in Xq28. However, no mutations were found in AVPR2 or its highly conserved flanking regions. Exome sequencing confirmed these findings and also revealed no deleterious variants in the provasopressin and aquaporin-2 genes. The 4 obligate female carriers osmo-regulated vasopressin in the low normal range. X-linked recessive transmission of DI can be due to a defect in either the secretion or the action of vasopressin. Other criteria are necessary to differentiate and manage the 2 disorders correctly.

Effect of liver resection-induced increases in hepatic venous pressure gradient on development of postoperative acute kidney injury

BackgroundThe impact of changes in portal pressure before and after liver resection (defined as ΔHVPG) on postoperative kidney function remains unknown. Therefore, we investigated the effect of ΔHVPG on (i) the incidence of postoperative AKI and (ii) the renin-angiotensin system (RAAS) and sympathetic nervous system (SNS) activity.MethodsWe included 30 patients undergoing partial liver resection. Our primary outcome was postoperative AKI according to KDIGO criteria. For our secondary outcome we assessed the plasma renin, aldosterone, noradrenaline, adrenaline, dopamine and vasopressin concentrations prior and 2 h after induction of anaesthesia, on the first and fifth postoperative day. HVPG was measured prior and immediately after liver resection.ResultsΔHVPG could be measured in 21 patients with 12 patients HVPG showing increases in HVPG (∆HVPG≥1 mmHg) while 9 patients remained stable. AKI developed in 7/12 of patients with increasing HVPG, but only in 2/9 of patients with stable ΔHVPG (p = 0.302). Noradrenalin levels were significantly higher in patients with increasing ΔHVPG than in patients with stable ΔHVPG. (p = 0.009). Biomarkers reflecting RAAS and SNS activity remained similar in patients with increasing vs. stable ΔHVPG.ConclusionsPatients with increased HVPG had higher postoperative creatinine concentrations, however, the incidence of AKI was similar between patients with increased versus stable HVPG.

Disrupted Circadian Control of Hormonal Rhythms and Anticipatory Thirst by Dim Light at Night.

Our study addresses underlying mechanisms of disruption of the circadian timing system by low-intensity artificial light at night (ALAN), which is a growing global problem, associated with serious health consequences. Rats were exposed to low-intensity (∼2 lx) ALAN for 2 weeks. Using in situ hybridization, we assessed 24-h profiles of clock and clock-controlled genes in the suprachiasmatic nuclei (SCN) and other hypothalamic regions, which receive input from the master clock. Moreover, we measured the daily rhythms of hormones within the main neuroendocrine axes as well as the detailed daily pattern of feeding and drinking behavior in metabolic cages. ALAN strongly suppressed the molecular clockwork in the SCN, as indicated by the suppressed rhythmicity in the clock (Per1, Per2, and Nr1d1) and clock output (arginine vasopressin) genes. ALAN disturbed rhythmic Per1 expression in the paraventricular and dorsomedial hypothalamic nuclei, which convey the circadian signals from the master clock to endocrine and behavioral rhythms. Disruption of hormonal output pathways was manifested by the suppressed and phase-advanced corticosterone rhythm and lost daily variations in plasma melatonin, testosterone, and vasopressin. Importantly, ALAN altered the daily profile in food and water intake and eliminated the clock-controlled surge of drinking 2 h prior to the onset of the rest period, indicating disturbed circadian control of anticipatory thirst and fluid balance during sleep. Our findings highlight compromised time-keeping function of the central clock and multiple circadian outputs, through which ALAN disturbs the temporal organization of physiology and behavior.

Effect of Angiotensin receptor blockade on Plasma Osmolality and Neurohumoral Responses to High Environmental Temperature in Rats Fed a High Salt Diet

Plasma osmolality (pOsmol) and neurohumoral signals play important roles in the pathophysiology of cardiovascular diseases. Our study investigated the effect of high environmental temperature (HET) on neurohumoral responses and pOsmol in rats fed a high salt diet (HSD), with and without angiotensin II receptor blockade (ARB), using telmisartan. Fifty-six male 8-week old Sprague-Dawley rats (95-110g) were randomly assigned into seven groups of 8 rats. These included control rats (I) fed with 0.3% NaCl diet (normal diet, ND); salt-loaded rats (II) fed with 8% NaCl (high salt) diet; ND rats (III) exposed to HET (38.5±0.5oC ) 4 hours daily per week; rats (IV) fed with 8% NaCl diet and exposed to HET daily. Others included rats (V) fed with 8% NaCl diet and treated with telmisartan (30mg/kg); ND rats (VI) exposed to HET and treated with telmisartan; rats (VI) fed with 8% NaCl diet, exposed to HET and treated with telmisartan. Plasma angiotensin II, aldosterone, vasopressin and norepinephrine (NE) concentrations were determined by ELISA technique; pOsmol from plasma K+, Na+ and Urea. HSD combined with HET in rats synergistically increased pOsmol (P&lt;0.001) with an associated non-synergistic rise in fluid intake (P&lt;0.001), fluid balance (P&lt;0.001), plasma angiotensin II (P&lt;0.01) and aldosterone (P&lt;0.05), NE (P&lt;0.001) and vasopressin (P&lt;0.05) concentrations compared to control. Telmisartan did not alter pOsmol in all the treated-rats, but normalized fluid intake levels and plasma vasopressin in the rats exposed to either HSD or HEt alone. Prolonged exposure of rats to hot environment exacerbated the effect of excess dietary salt on pOsmol, with no effect on angiotensin II-mediated neurohumoral responses

Effect of Angiotensin receptor blockade on Plasma Osmolality and Neurohumoral Responses to High Environmental Temperature in Rats Fed a High Salt Diet.

Plasma osmolality (pOsmol) and neurohumoral signals play important roles in the pathophysiology of cardiovascular diseases. Our study investigated the effect of high environmental temperature (HET) on neurohumoral responses and pOsmol in rats fed a high salt diet (HSD), with and without angiotensin II receptor blockade (ARB), using telmisartan. Fifty-six male 8-week old Sprague-Dawley rats (95-110g) were randomly assigned into seven groups of 8 rats. These included control rats (I) fed with 0.3% NaCl diet (normal diet, ND); salt-loaded rats (II) fed with 8% NaCl (high salt) diet; ND rats (III) exposed to HET (38.5±0.5oC ) 4 hours daily per week; rats (IV) fed with 8% NaCl diet and exposed to HET daily. Others included rats (V) fed with 8% NaCl diet and treated with telmisartan (30mg/kg); ND rats (VI) exposed to HET and treated with telmisartan; rats (VI) fed with 8% NaCl diet, exposed to HET and treated with telmisartan. Plasma angiotensin II, aldosterone, vasopressin and norepinephrine (NE) concentrations were determined by ELISA technique; pOsmol from plasma K+, Na+ and Urea. HSD combined with HET in rats synergistically increased pOsmol (P<0.001) with an associated non-synergistic rise in fluid intake (P<0.001), fluid balance (P<0.001), plasma angiotensin II (P<0.01) and aldosterone (P<0.05), NE (P<0.001) and vasopressin (P<0.05) concentrations compared to control. Telmisartan did not alter pOsmol in all the treated-rats, but normalized fluid intake levels and plasma vasopressin in the rats exposed to either HSD or HEt alone. Prolonged exposure of rats to hot environment exacerbated the effect of excess dietary salt on pOsmol, with no effect on angiotensin II-mediated neurohumoral responses.

Apelin and Vasopressin: The Yin and Yang of Water Balance.

Apelin, a (neuro)vasoactive peptide, plays a prominent role in controlling body fluid homeostasis and cardiovascular functions. Experimental data performed in rodents have shown that apelin has an aquaretic effect via its central and renal actions. In the brain, apelin inhibits the phasic electrical activity of vasopressinergic neurons and the release of vasopressin from the posterior pituitary into the bloodstream and in the kidney, apelin regulates renal microcirculation and counteracts in the collecting duct, the antidiuretic effect of vasopressin occurring via the vasopressin receptor type 2. In humans and rodents, if plasma osmolality is increased by hypertonic saline infusion/water deprivation or decreased by water loading, plasma vasopressin and apelin are conversely regulated to maintain body fluid homeostasis. In patients with the syndrome of inappropriate antidiuresis, in which vasopressin hypersecretion leads to hyponatremia, the balance between apelin and vasopressin is significantly altered. In order to re-establish the correct balance, a metabolically stable apelin-17 analog, LIT01-196, was developed, to overcome the problem of the very short half-life (in the minute range) of apelin in vivo. In a rat experimental model of vasopressin-induced hyponatremia, subcutaneously (s.c.) administered LIT01-196 blocks the antidiuretic effect of vasopressin and the vasopressin-induced increase in urinary osmolality, and induces a progressive improvement in hyponatremia, suggesting that apelin receptor activation constitutes an original approach for hyponatremia treatment.

The role of Cushing’s reflex and the vasopressin-mediated oligoanuric response to intracranial hypertension in patients with abdominal compartment syndrome

BackgroundWe examined the link between increased intra-abdominal pressure, intracranial pressure, and vasopressin release as a potential mechanism. Intra-abdominal pressure, produced by abdominal-cavity insufflation with carbon dioxide (CO2) during laparoscopic abdominal procedures to facilitate visualization, is associated with various complications, including arterial hypertension and oliguria. MethodsMean arterial pressure, optic nerve sheath diameter, measured as a proxy for intracranial pressure, plasma vasopressin, serum and urine osmolarity, and urine output were measured 4 times during laparoscopic sleeve gastrectomy in 42 patients: before insufflation with CO2 (T0); after insufflation to 15 cm water (H2O) pressure, with 5 cm H2O positive end-expiratory pressure (T1); after positive end-expiratory pressure was raised to 10 cm H2O (T2); and after a return to the baseline state (T3). Mean values at T0 to T3 and the directional consistency of changes (increase/decrease/ unchanged) were compared among the 4 data-collection points. ResultsStatistically significant elevations (all P ≤ .001) were noted from T0 to T1 and from T0 to T2 in mean arterial pressure, optic nerve sheath diameter, and vasopressin, followed by decreases at T3. For optic nerve sheath diameter and vasopressin, the increases at T1 and T2 occurred in 98% and 100% of patients, ultimately exceeding normal levels in 88 and 97%, respectively. Conversely, urine output fell from T0 to T1 and T2 by 60.9 and 73.4%, decreasing in 88.1% of patients (all P < .001). Patients with class II obesity exhibited statistically greater increases in optic nerve sheath diameter and vasopressin, but statistically less impact on urine output, than patients with class III obesity. ConclusionIncreased mean arterial pressure, intracranial pressure, and vasopressin release appear to be intermediary steps between increased intra-abdominal pressure and oliguria. Further research is necessary to determine any causative links between these physiological changes.

Endolymphatic Sac Drainage Surgery and Plasma Stress Hormone Vasopressin Levels in Meniere's Disease.

Meniere's disease is a common inner ear disorder accompanied by vertigo attacks and fluctuating hearing loss that some believe is due to a stressful lifestyle. To elucidate the scientific relationship in neuro-endocrinology between Meniere's disease and stress, we examined the surgical results of endolymphatic sac drainage surgery and changes in stress-induced plasma arginine-vasopressin levels. We enrolled 100 intractable Meniere's patients and examined surgical results and plasma vasopressin levels. Fifty-four chronic otitis media patients who underwent tympano-mastoidectomy formed a control group. We assessed surgical results during a 2-year follow-up period, including vertigo and hearing loss. We examined plasma vasopressin levels just before surgery and 1 week, 1 year, and 2 years after surgery. In patients with intractable Meniere's disease, plasma vasopressin levels were significantly reduced 1 week after surgery compared to the decrease observed in chronic otitis media patients after tympano-mastoidectomy. In intractable Meniere's disease, long-lasting low plasma vasopressin levels after surgery were associated with significantly good surgical results. In recurrent Meniere's disease, a gradual plasma vasopressin level elevation was observed after surgery, followed by recurrent vertigo attacks and sensorineural hearing loss. It is suggested that long-lasting high levels of plasma vasopressin could have adverse effects on inner ear water metabolism and the subsequent Meniere's disease symptoms. Effective treatments for Meniere's disease might be best based on the maintenance of low plasma vasopressin levels.

Hemodynamic phenotyping of transgenic rats with ubiquitous expression of an angiotensin-(1-7)-producing fusion protein.

Activation of the angiotensin (Ang)-converting enzyme (ACE) 2/Ang-(1-7)/MAS receptor pathway of the renin-angiotensin system (RAS) induces protective mechanisms in different diseases. Herein, we describe the cardiovascular phenotype of a new transgenic rat line (TG7371) that expresses an Ang-(1-7)-producing fusion protein. The transgene-specific mRNA and the corresponding protein were shown to be present in all evaluated tissues of TG7371 with the highest expression in aorta and brain. Plasma Ang-(1-7) levels, measured by radioimmunoassay (RIA) were similar to control Sprague-Dawley (SD) rats, however high Ang-(1-7) levels were found in the hypothalamus. TG7371 showed lower baseline mean arterial pressure (MAP), assessed in conscious or anesthetized rats by telemetry or short-term recordings, associated with increased plasma atrial natriuretic peptide (ANP) and higher urinary sodium concentration. Moreover, evaluation of regional blood flow and hemodynamic parameters with fluorescent microspheres showed a significant increase in blood flow in different tissues (kidneys, mesentery, muscle, spleen, brown fat, heart and skin), with a resulting decrease in total peripheral resistance (TPR). TG7371 rats, on the other hand, also presented increased cardiac and global sympathetic tone, increased plasma vasopressin (AVP) levels and decreased free water clearance. Altogether, our data show that expression of an Ang-(1-7)-producing fusion protein induced a hypotensive phenotype due to widespread vasodilation and consequent fall in peripheral resistance. This phenotype was associated with an increase in ANP together with an increase in AVP and sympathetic drive, which did not fully compensate the lower blood pressure (BP). Here we present the hemodynamic impact of long-term increase in tissue expression of an Ang-(1-7)-fusion protein and provide a new tool to investigate this peptide in different pathophysiological conditions.

N-Methyl-D-aspartate Glutamate Receptor Modulates Cardiovascular and Neuroendocrine Responses Evoked by Hemorrhagic Shock in Rats.

Here, we report the participation of N-methyl-D-aspartate (NMDA) glutamate receptor in the mediation of cardiovascular and circulating vasopressin responses evoked by a hemorrhagic stimulus. In addition, once NMDA receptor activation is a prominent mechanism involved in nitric oxide (NO) synthesis in the brain, we investigated whether control of hemorrhagic shock by NMDA glutamate receptor was followed by changes in NO synthesis in brain supramedullary structures involved in cardiovascular and neuroendocrine control. Thus, we observed that intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK801, 0.3 mg/kg) delayed and reduced the magnitude of hemorrhage-induced hypotension. Besides, hemorrhage induced a tachycardia response in the posthemorrhage period (i.e., recovery period) in control animals, and systemic treatment with MK801 caused a bradycardia response during hemorrhagic shock. Hemorrhagic stimulus increased plasma vasopressin levels during the recovery period and NMDA receptor antagonism increased concentration of this hormone during both the hemorrhage and postbleeding periods in relation to control animals. Moreover, hemorrhagic shock caused a decrease in NOx levels in the paraventricular nucleus of the hypothalamus (PVN), amygdala, bed nucleus of the stria terminalis (BNST), and ventral periaqueductal gray matter (vPAG). Nevertheless, treatment with MK801 did not affect these effects. Taken together, these results indicate that the NMDA glutamate receptor is involved in the hemorrhagic shock by inhibiting circulating vasopressin release. Our data also suggest a role of the NMDA receptor in tachycardia, but not in the decreased NO synthesis in the brain evoked by hemorrhage.

Antidiuretic hormone and the activation of glucose production during high intensity aerobic exercise

ObjectiveThis study aimed to investigate the role that antidiuretic hormone (ADH) may play in the activation of glucose production during high intensity aerobic exercise. Materials/methodsThis study was part of larger study based on a repeated measures cross-over study design and involved ten adult participants who exercised in the morning at 80 % V̇O2peak for up to 40 min or until exhaustion. During and after exercise, the participants were subjected to a morning euglycaemic/euinsulinaemic clamp while [6,6-2H2]glucose was infused and blood sampled to measure the endogenous rate of glucose appearance (Ra) and ADH levels. ResultsThe levels of plasma ADH were 1.8 ± 0.2 pmol/L (mean ± SEM) at rest and increased to 10.5 ± 2.1 pmol/L at the end of exercise (mean ± SEM), which lasted 8.5–40 min. In response to exercise, glucose Ra also rose significantly (p < 0.05), but there was no significant association between changes in ADH levels and glucose Ra (r = 0.49; p = 0.150). ConclusionsAlthough the significant increase in glucose Ra and ADH levels during high intensity aerobic exercise suggest for the first time that these processes may be causally related, there was no significant association between these variables, maybe because of the small sample size and varying exercise durations. Hence, the importance of the causal role that ADH may play in the exercise-mediated activation of hepatic glucose production warrants further in depth investigations.

Prolonged efavirenz exposure reduces peripheral oxytocin and vasopressin comparable to known drugs of addiction in male Sprague Dawley rats.

IntroductionSeveral drugs of abuse (DOA) are capable of modulating neurohypophysial hormones, such as oxytocin (OT) and vasopressin (VP), potentially resulting in the development of psychological abnormalities, such as cognitive dysfunction, psychoses, and affective disorders. Efavirenz (EFV), widely used in Africa and globally to treat HIV, induces diverse neuropsychiatric side effects while its abuse has become a global concern. The actions of EFV may involve neurohypophysial system (NS) disruption like that of known DOA. This study investigated whether sub-chronic EFV exposure, at a previously-determined rewarding dose, alters peripheral OT and VP levels versus that of a control, ∆9-tetrahydrocannabinol (∆9-THC), methamphetamine (MA) and cocaine.Materials and methodsTo simulate the conditions under which reward-driven behavior had previously been established for EFV, male Sprague Dawley rats (n = 16/exposure) received intraperitoneal vehicle (control) or drug administration across an alternating sixteen-day dosing protocol. Control administration (saline/olive oil; 0.2 ml) occurred on odd-numbered and drug administration (EFV: 5 mg/kg, ∆9-THC: 0.75 mg/kg, MA: 1 mg/kg, or cocaine: 20 mg/kg) on even-numbered days followed by euthanasia, trunk blood collection and plasma extraction for neuropeptide assay. Effect of drug exposure on peripheral OT and VP levels was assessed versus controls and quantified using specific ELISA kits. Statistical significance was determined by Kruskal-Wallis ANOVA, with p < 0.05. Ethics approval: NWU-00291-17-A5.ResultsDelta-9-THC reduced OT and VP plasma levels (p < 0.0001, p = 0.0141; respectively), cocaine reduced plasma OT (p = 0.0023), while MA reduced plasma VP levels (p = 0.0001), all versus control. EFV reduced OT and VP plasma levels (p < 0.0001; OT and VP) versus control, and similar to ∆9-THC.ConclusionEFV markedly affects the NS in significantly reducing both plasma OT and VP equivalent to DOA. Importantly, EFV has distinct effects on peripheral OT and VP levels when assessed within the context of drug dependence. The data highlights a possible new mechanism underlying previously documented EFV-induced effects in rats, and whereby EFV may induce neuropsychiatric adverse effects clinically; also providing a deeper understanding of the suggested abuse-potential of EFV.

Neuroendocrine changes in the hypothalamic-neurohypophysial system in the Wistar audiogenic rat (WAR) strain submitted to audiogenic kindling.

The Wistar audiogenic rat (WAR) strain is used as an animal model of epilepsy, which when submitted to acute acoustic stimulus presents tonic-clonic seizures, mainly dependent on brainstem (mesencephalic) structures. However, when WARs are exposed to chronic acoustic stimuli (audiogenic kindling-AK), they usually present tonic-clonic seizures, followed by limbic seizures, after recruitment of forebrain structures such as the cortex, hippocampus and amygdala. Although some studies have reported that hypothalamic-hypophysis function is also altered in WAR through modulating vasopressin (AVP) and oxytocin (OXT) secretion, the role of these neuropeptides in epilepsy still is controversial. We analyzed the impact of AK and consequent activation of mesencephalic neurocircuits and the recruitment of forebrain limbic (LiR) sites on the hypothalamic-neurohypophysial system and expression of Avpr1a and Oxtr in these structures. At the end of the AK protocol, nine out of 18 WARs presented LiR. Increases in both plasma vasopressin and oxytocin levels were observed in WAR when compared to Wistar rats. These results were correlated with an increase in the expressions of heteronuclear (hn) and messenger (m) RNA for Oxt in the paraventricular nucleus (PVN) in WARs submitted to AK that presented LiR. In the paraventricular nucleus, the hnAvp and mAvp expressions increased in WARs with and without LiR, respectively. There were no significant differences in Avp and Oxt expression in supraoptic nuclei (SON). Also, there was a reduction in the Avpr1a expression in the central nucleus of the amygdala and frontal lobe in the WAR strain. In the inferior colliculus, Avpr1a expression was lower in WARs after AK, especially those without LiR. Our results indicate that both AK and LiR in WARs lead to changes in the hypothalamic-neurohypophysial system and its receptors, providing a new molecular basis to better understaind epilepsy.

Dehydration results in a reduction in the expression and function of AT 1 R and V 1 R in resistance‐sized arteries

In the body, the state of dehydration occurs where there is a deficit of water compared to that which is required to function properly. Water transportation is crucial and carried out via aquaporins (AQPs) located throughout the body and as a response to dehydration events, hormones such as angiotensin II (Ang II) and arginine-vasopressin (AVP) are secreted to induce various normal physiological functions via a hormone-specific receptor and associated-receptor activation found in vascular smooth muscle cells (VSMCs). Consequently, dehydration results with overall blood vessel constriction and thickening of the blood, ultimately leading to heart strain and increased blood pressure. Currently, the effect of dehydration on both the angiotensin II receptor type 1 (AT1R) and vasopressin receptor (V1R) expressed in resistance-sized artery VSMCs is unclear. C57BL/6J male mice were deprived of water for 48 hours before analyzing AT1R and V1R expression and function in freshly isolated mesenteric arteries, compared to controls. Dehydration for 48 hours results in a reduction in AT1R and V1R message and protein expression as well as a reduction in angiotensin- and arginine vasopressin (AVP)-induced vasoconstriction in pressurized mesenteric arteries. These data suggest that AT1R and V1R function is reduced in resistance-sized mesenteric arteries as a response to an elevation in plasma vasopressin and angiotensin II that occurs after dehydration.

PENDRIN REDUCTION IS ASSOCIATED WITH ACUTE INTRAVENOUS SODIUM CHLORIDE LOADING IN PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism (PA) is a common, potentially curable form of hypertension characterised by excessive, autonomous aldosterone production. In the distal renal tubule, aldosterone is involved in volume homeostasis by modulation of NaCl reabsorption via the epithelial Na+ channel (ENaC), the NaCl cotransporter (NCC) and the Cl-/HCO3- exchanger (pendrin). Na+ loading suppresses plasma aldosterone but its effects on these proteins in humans remain unclear. Design and method: Urine samples were collected before and 1 h after a 4 h 2L 0.9% saline infusion from 13 (F9/M5) subjects including 10 confirmed with PA and 3 in which PA was excluded [herein designated low renin hypertension (LRH)]. Urinary exosomes were harvested by ultracentrifugation and analysed by LC-MS/MS. Results: Plasma aldosterone decreased (P &lt; 0.05) from 623 [312, 2210] (median [range]) to 338 [197, 2330] pmol/L in confirmed PA and from 223 [180, 256] to 117 [110, 133] pmol/L in LRH. There were no changes in plasma K+ (pre 3.4 [2.6, 4.3] vs post 3.6 [2.6, 3.9] mmol/L in PA; pre 4.1 [3.6, 4.1] vs post 4.0 [3.9, 4.0] mmol/L in LRH). LC-MS/MS demonstrated decreases in abundance of pendrin (21.5%, P &lt; 0.01) and aquaporin-2 (AQP2) (42.9%, P &lt; 0.01) in urinary exosomes and a trend towards a decrease in NCC (20%, P = 0.07) in patients with PA. No changes were seen in those with LRH. PA patients had higher baseline pendrin abundance (1.2 [1.0, 2.1]) than LRH patients (0.7 [0.5, 1.0]) (P &lt; 0.05), but there was no difference in baseline AQP2. In all 13 subjects combined, baseline pendrin correlated positively with plasma aldosterone (P = 0.02, r2 = 0.32) and negatively with plasma K+ (P = 0.02, r2 = 0.35), whilst no correlations were observed between AQP2 and aldosterone or K+. Delta Pendrin (P = 0.04, r2 = 0.3) and delta AQP2 (P = 0.01, r2 = 0.58) positively correlated with delta plasma aldosterone. Conclusions: In PA, reduction in pendrin during saline infusion may be due to falling plasma aldosterone in response to NaCl loading. Although also correlating with reduction in aldosterone, a more likely explanation for the reduction in AQP2 may be a fall in plasma vasopressin induced by water loading. Different observations in LRH require validation with larger numbers.

Angiotensin II-Vasopressin Interactions in The Regulation of Cardiovascular Functions. Evidence for an Impaired Hormonal Sympathetic Reflex in Hypertension and Congestive Heart Failure.

Angiotensin II (ANG II) and vasopressin (VP) interact in several physiological mechanisms, playing a role in arterial hypertension and congestive heart failure. Aim and Methods of Search: To overview the primary mechanism involved in the regulation of cardiovascular function, PubMed/Medline was searched, and authors selected original articles and reviews written in English. Angiotensin II (ANG II) and vasopressin (VP) are involved in several physiological mechanisms. ANG II stimulates VP release via angiotensin receptor 1. ANG II and VP stimulate aldosterone synthesis and secretion and enhance its action at the renal collecting duct level. VP is also involved in the cardiovascular reflex control of the sympathetic nervous system (SNS). Also, VP potentiates vasoconstriction and cardiac contractility, enhancing the effect of ANG II on sympathetic tone and arterial pressure. On the other hand, ANG II and VP act antagonistically in regulating baroreflex control of the SNS. There is evidence that high VP plasma levels increase baroreflex sympatho-inhibitory responses, and the arterial baroreflex response is shifted to lower pressure. This cardiovascular reflex control is mediated mainly in the brain, specifically in the circumventricular organ area postrema (AP). The modulation of cardiovascular reflex control induced by VP is abolished after lesions of the AP. VP modulation of baroreflex function is also under the control of α2-adrenergic pathway arising from the nucleus of the solitary tract (NTS) and synapsing on VP-ergic neurons of supraoptic and paraventricular nuclei. Presynaptic α2-adrenergic stimulation within the NTS inhibits VP release induced by hypovolemia and the effects of VP and AP on baroreflex control of SNS, thus showing baroreceptor afferent inputs are processed within the NTS and contribute to the increased baroreflex sympatho-inhibitory responses. In patients with congestive heart failure (CHF), plasma VP levels are elevated, inducing an up-regulation of aquaporin 2 water channel expression in renal collecting duct (CD) cells provoking exaggerated water retention and dilutional hyponatremia. Antagonists of VP and ANG II receptors reduce edema, body weight, and dyspnea in CHF patients. Hormonal imbalance between ANG II, VP, and SNS may induce hypertension and impaired water-electrolyte balance in cardiovascular diseases.

Involvement of Supraoptic Astrocytes in Basilar Artery Occlusion-Evoked Differential Activation of Vasopressin Neurons and Vasopressin Secretion in Rats.

Vasopressin (VP) is a key factor in the development of brain injury in ischemic stroke. However, the regulation of VP secretion in basilar artery occlusion (BAO) remains unclear. To clarify the regulation of VP secretion in BAO and the underlying mechanisms, we performed this study in a rat model of BAO with (BC) or without common carotid artery occlusion (CCAO). The results showed that BAO and BC time-dependently increased neurological scores and that BC also increased water contents in the medulla at 2h and in the pontine at 8h. Moreover, plasma VP level increased significantly at BAO-8h, CCAO and BC-2h but not at BC-8h; however, VP expressions increased in the supraoptic nucleus (SON) at BC-8h. The neurological scores were highly correlated with pontine water contents and plasma VP levels. The number of phosphorylated extracellular signal-regulated protein kinase1/2-positive VP neurons increased significantly in the SON at BC-8h. Similarly, the number of c-Fos-positive VP neurons increased significantly in the SON at BAO-8h and BC-8h. In addition, the length of glial fibrillary acidic protein (GFAP) filaments increased significantly in BC compared to BAO only. Aquaporin 4 (AQP4) puncta around VP neurons increased significantly at BC-8h relative to BC-2h, which had negative correlation with plasma VP levels. These findings indicate that BAO facilitates VP secretion and increases VP neuronal activity in the SON. The peripheral VP release is possibly under a negative feedback regulation of central VP neuronal activity through increasing GFAP and AQP4 expression in astrocytic processes.