Plasma Vasopressin Concentration Research Articles

Vasopressin and cardiovascular autonomic adjustment in chronic hypertensive pregnancy

Chronic hypertensive pregnancy (CHP) is a growing health issue with unknown etiology. Vasopressin (VP), a nonapeptide synthesized in paraventricular (PVN) and supraoptic nucleus (SON), is a well-known neuroendocrine and autonomic modulator of the cardiovascular system, related to hypertension development. We quantified gene expression of VP and its receptors, V1aR and V1bR, within the PVN and SON in CHP and normal pregnancy, and assessed levels of secreted plasma VP. Also, we evaluated autonomic cardiovascular adaptations to CHP using spectral indices of blood pressure (BPV) and heart rate (HRV) short-term variability, and spontaneous baroreflex sensitivity (BRS). Experiments were performed in female spontaneously hypertensive rats (SHRs) and in normotensive Wistar rats (WRs). Animals were equipped with a radiotelemetry probe for continuous hemodynamic recordings before and during pregnancy. BPV, HRV and BRS were assessed using spectral analysis and the sequence method, respectively. Plasma VP was determined by ELISA whilst VP, V1aR, and V1bR gene expression was analyzed by real-time-quantitative PCR (RT-qPCR). The results show that non-pregnant SHRs exhibit greater VP, V1aR, and V1bR gene expression in both PVN and SON respectively, compared to Wistar dams. Pregnancy decreased VP gene expression in the SON of SHRs but increased it in the PVN and SON of WRs. Pregnant SHRs exhibited a marked drop in plasma VP concentration associated with BP normalization. This triggered marked tachycardia, heart rate variability increase, and BRS increase in pregnant SHRs. It follows that regardless of BP normalization in late pregnancy, SHRs exhibit cardiovascular vulnerability and compensate by recruiting vagal mechanisms.Pregnant SHR dams have reduced expression of VP in SON associated with increased V1bR expression, lower plasma VP, normal BP during late pregnancy and marked signs of enhanced sympathetic cardiac stimulation (increased HR and LFHR variability) and recruitment of vagal mechanisms (enhancement of BRS and HFHR variability).

Long-term health outcomes associated with hydration status.

Body water balance is determined by fundamental homeostatic mechanisms that maintain stable volume, osmolality and the composition of extracellular and intracellular fluids. Water balance is maintained by multiple mechanisms that continuously match water losses through urine, the skin, the gastrointestinal tract and respiration with water gains achieved through drinking, eating and metabolic water production. Hydration status is determined by the state of the water balance. Underhydration occurs when a decrease in body water availability, due to high losses or low gains, stimulates adaptive responses within the water balance network that are aimed at decreasing losses and increasing gains. This stimulation is also accompanied by cardiovascular adjustments. Epidemiological and experimental studies have linked markers of low fluid intake and underhydration - such as increased plasma concentration of vasopressin and sodium, as well as elevated urine osmolality - with an increased risk of new-onset chronic diseases, accelerated aging and premature mortality, suggesting that persistent activation of adaptive responses may be detrimental to long-term health outcomes. The causative nature of these associations is currently being tested in interventional trials. Understanding of the physiological responses to underhydration may help to identify possible mechanisms that underlie potential adverse, long-term effects of underhydration and inform future research to develop preventative and treatment approaches to the optimization of hydration status.

Input from afferent renal nerves is involved in progression of hypertensive heart failure through central vasopressin-mediated sympathoexcitation

Introduction: Paraventricular nucleus of hypothalamus (PVN), a control center of sympathetic outflow, receives the input from afferent renal nerves. Although acute stimulation of afferent renal nerves increases central sympathetic outflow, it remains unclear if the renal afferents contribute to progression of heart failure. Acute stimulation of afferent renal nerves was reported to increase plasma vasopressin concentration. In addition, central dendritic release of vasopressin by activation of vasopressin-expressing neurons located in the PVN may cause sympathoexcitation via stimulation of neighboring presympathetic neurons in the PVN. Therefore, we hypothesized that the chronic input from afferent renal nerves contributes to sympathoexcitation and hypertensive cardiac dysfunction along with activation of vasopressin-expressing neurons and presympathetic neurons in the PVN. Methods: Male Dahl salt-sensitive rats were fed low salt diet (LS) or 8% high salt diet from 6 weeks of age, and the high salt-fed rats were allocated to selective afferent renal denervation (HS-ARDN) or sham surgery (HS-Sham) at 9 weeks. The effect of ARDN on central sympathetic regulation was investigated at 12 weeks (pre-heart failure phase). In another cohort, its effect on cardiac phenotypes was evaluated at 16 weeks (heart failure phase). Results: At 12 weeks, plasma norepinephrine level was increased in HS-Sham compared to LS and was attenuated by ARDN (LS 188.7±16.5 pg/ml, HS-Sham 563.8±82.7 pg/ml, HS-ARDN 327.4±50.2 pg/ml; n=15, 12, 14; p<0.05). The c-Fos expression, a marker of neuronal activity, in presympathetic neurons in the PVN was also increased in HS-Sham and attenuated in HS-ARDN, which was in parallel with the c-Fos expression in vasopressin-expressing neurons in the PVN. At 16 weeks, the decrease of left ventricular (LV) fractional shortening (HS-Sham 25.9±1.7 % vs LS 46.7±0.6 %, n=9, 9; p<0.01) was improved in HS-ARDN (42.2±1.2 %, n=7; p<0.01 vs HS-Sham). LV weight and lung weight were significantly increased in HS-Sham compared to LS (LV weight/body weight: 4.39±0.19 mg/g vs 2.53±0.03 mg/g; lung weight/body weight: 5.29±0.37 mg/g vs 3.55±0.05 mg/g; p<0.05), and these changes were attenuated in HS-ARDN (LV weight/body weight: 3.73±0.14 mg/g; lung weight/body weight: 4.17±0.11 mg/g; p<0.05 vs HS-Sham). Histological LV fibrosis and fibrosis marker expression, such as connective tissue growth factor, in LV were significantly attenuated in HS-ARDN compared to HS-Sham. ARDN did not significantly impact the high salt-induced blood pressure elevation in both cohorts. Conclusion: The input from afferent renal nerves contributes to cardiac dysfunction, probably via the central vasopressin-mediated sympathoexcitation even without blood pressure changes in hypertensive heart failure model. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Reducing Venous Return Using BFR: Alterations In Blood Volume Regulating Hormones And Short-term Training Responses

Partitioning blood from central circulation to the legs via blood flow restricted (BFR) exercise will impact venous return acutely, though the relationship between occlusion pressure and reduced venous return is unknown. A reduction in central volume, which can be tracked by measuring ventricular filling, is likely to affect renin and anti-diuretic hormone (ADH) concentrations, that regulate blood volume via water retention. Blood volume has a strong influence on maximal aerobic capacity (VO2max); thus, BFR exercise training could augment aerobic capacity when performed repeatedly. PURPOSE: To determine the impact of BFR during and following exercise on ventricular filling, hormone release, and training response. METHODS: Venous return was estimated via ultrasound measures of inferior vena cava diameter (IVCD) and end-diastolic volume (EDV) while participants (n = 13) had tourniquets inflated around their upper thigh during and following semi-recumbent cycling. Graded occlusion pressures were tested in each exercise condition to determine the greatest reduction in venous return and these pressures were used in two separate 2-week BFR training models: 1) BFR during walking (20 min) and 2) BFR following sprint cycling (5x10s). For both styles of BFR exercise, the hormonal response to a single training bout was analyzed using pre/post blood draws with VO2max measured before and after training. RESULTS: Compared to the control, BFR effectively reduced venous return during exercise at 100% arterial occlusion pressure (IVCD 15%; EDV 11%, both p < 0.05) and at 75% occlusion pressure during recovery (IVCD 20%; EDV 18%, both p < 0.02). Increased plasma renin and ADH concentrations were observed following exercise (pooled, p < 0.05) for BFR during walking (renin: 19.6 ± 9.4 to 40.8 ± 16.7 ng/L; ADH: 6.3 ± 4.1 to 28.5 ± 30.8 pmol/L) and post sprint exercise (renin: 24.2 ± 14.9 to 121 ± 72.7 ng/L; ADH:7.1 ± 3.4 to 374.1 ± 311 pmol/L). Following two weeks of training with BFR during walking, absolute VO2max improved (6.8 ± 6.4%) but was unchanged in the post exercise BFR model, with large inter-individual variability. CONCLUSION: Reducing venous return via leg BFR leads to increases in circulating blood-volume regulating hormones. Preliminary work suggests BFR during exercise results in greater changes in VO2max.

Neuroendocrine hormone status and diuretic response to atrial natriuretic peptide in patients with acute heart failure.

Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a fundamental action of ANP in acute heart failure (AHF), whereas the diuretic effect of ANP is different in each patient according to the diversity of renal response to ANP, which is affected by baseline plasma ANP status and deficiency of circulating ANP. Meanwhile, associations between other neuroendocrine hormones and the diuretic response to ANP are unclear. This study investigated the impact of pivotal neuroendocrine hormones on the diuretic effects of exogenous ANP, carperitide. Plasma ANP, renin, aldosterone, and vasopressin levels and the diuretic effect of 0.0125μg/kg/min of carperitide alone for the first 6h were prospectively evaluated in 75 patients with AHF. Lower ANP levels were significantly associated with a greater diuretic response to exogenous ANP (r=-0.35, P=0.002). Additionally, higher vasopressin levels were significantly related to the poor diuretic effects of exogenous ANP (r=-0.54, P<0.001). Plasma ANP and vasopressin concentrations were not significantly correlated (r=0.19, P=0.10). Baseline systolic blood pressure, renal function, and prior use of loop diuretics did not predict the diuretic response to exogenous ANP, whereas vasopressin levels independently predicted a diuretic response to exogenous ANP (P<0.001), as well as lower plasma ANP levels (P=0.027). Vasopressin status was significantly associated with the diuretic response to exogenous ANP in AHF, independent of plasma ANP status. The results may provide a better understanding of the actions of sacubitril/valsartan.

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.

A Comparison of Urine Dilution Ability between Adult Dominant Polycystic Kidney Disease, Other Chronic Kidney Diseases, and Healthy Control Subjects: A Case-Control Study.

The final dilution of urine is regulated via aquaporin-2 water channels in the distal part of the nephron. It is unclear whether urine dilution ability in autosomal dominant polycystic kidney disease patients (ADPKD patients) differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine dilution ability in ADPKD patients compared to non-ADPKD patients and healthy controls. Methods. Eighteen ADPKD, 16 non-ADPKD patients (both with chronic kidney disease, stage I-IV), and 18 healthy controls received an oral water load of 20 ml/kg body weight. Urine was collected in 7 consecutive periods. We measured free water clearance (CH2O), urine osmolality, urine output, fractional excretion of sodium, urine aquaporin2 (u-AQP2), and urine epithelial sodium channel (u-ENaC). Blood samples were drawn four times (at baseline, 2 h, 4 h, and 6 hours after the water load) for analyses of plasma osmolality, vasopressin, renin, angiotensin II, and aldosterone. Brachial and central blood pressure was measured regularly during the test. Results. The three groups were age and gender matched, and the patient groups had similar renal function. One hour after water load, the ADPKD patients had an increased CH2O compared to non-ADPKD patients (2.97 ± 2.42 ml/min in ADPKD patients vs. 1.31 ± 1.50 ml/min in non-ADPKD patients, p0.029). The reduction in u-AQP2 and u-ENaC occurred earlier in ADPKD than in non-ADPKD patients. Plasma concentrations of vasopressin, renin, angiotensin II, and aldosterone and blood pressure measurements did not show any differences that could explain the deviation in urine dilution capacity between the patient groups. Conclusions. ADPKD patients had a higher CH2O than non-ADPKD patients after an oral water load, and u-AQP2 and u-ENaC were more rapidly reduced than in non-ADPKD patients. Thus, urine-diluting capacity may be better preserved in ADPKD patients than in non-ADPKD patients.

Aspects regarding renal morphophysiology of fruit-eating and vampire bats

Bats have adapted to many different feeding habits, which are known to induce morphophysiological adaptations in several tissues, especially those particularly involved with absorption, metabolism and excretion. The common vampire bat (Desmodus rotundus) has a very unique diet (blood), which, among other challenges, seems to pose a risk to their kidneys, due to the increased nitrogen excretion imposed by their remarkably high protein meal. Fruit-eating bats (Artibeus lituratus) consume a high carbohydrate diet and may be taken as a suitable species for this dietary comparative study. Here we aimed at investigating the renal morphology and stereology, kidneys antioxidant capacity, and plasma antidiuretic hormone (ADH) concentrations in adult fruit-eating and vampire bats. Sixteen animals were captured and used in this study, being 8 adult males from each species. Our results showed higher morphological standards of glomerular area, volumetric density of glomeruli, and renal somatic index for vampire bats, as well as higher reactive species of oxygen (ROS) production, such as nitric oxide (NO), higher plasma iron reduction ability (FRAP), higher activity of the antioxidant enzyme glutathione-S-transferase (GST) and a higher malondialdehyde production (MDA) in vampires’ kidneys, compared to the fruit-eating species. The activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were higher in fruit-eating bats. Plasma ADH concentrations were not different between species. Taken together, the renal morphophysiology conditions presented by vampire bats might be associated with a high demand for nitrogenous products excretion imposed by protein and iron overload. These features may play an important role on preventing protein-overload nephropathy, allowing vampires to survive under such a unique diet.

Lixivaptan, a New Generation Diuretic, Counteracts Vasopressin-Induced Aquaporin-2 Trafficking and Function in Renal Collecting Duct Cells.

Vasopressin V2 receptor (V2R) antagonists (vaptans) are a new generation of diuretics. Compared with classical diuretics, vaptans promote the excretion of retained body water in disorders in which plasma vasopressin concentrations are inappropriately high for any given plasma osmolality. Under these conditions, an aquaretic drug would be preferable over a conventional diuretic. The clinical efficacy of vaptans is in principle due to impaired vasopressin-regulated water reabsorption via the water channel aquaporin-2 (AQP2). Here, the effect of lixivaptan—a novel selective V2R antagonist—on the vasopressin-cAMP/PKA signaling cascade was investigated in mouse renal collecting duct cells expressing AQP2 (MCD4) and the human V2R. Compared to tolvaptan—a selective V2R antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia—lixivaptan has been predicted to be less likely to cause liver injury. In MCD4 cells, clinically relevant concentrations of lixivaptan (100 nM for 1 h) prevented dDAVP-induced increase of cytosolic cAMP levels and AQP2 phosphorylation at ser-256. Consistent with this finding, real-time fluorescence kinetic measurements demonstrated that lixivaptan prevented dDAVP-induced increase in osmotic water permeability. These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of lixivaptan and suggest that lixivaptan has the potential to become a safe and effective therapy for the treatment of disorders characterized by high plasma vasopressin concentrations and water retention.

Vasopressin Plasma Concentrations Are Not Associated with Hemodynamic Response to Exogenous Vasopressin for Septic Shock.

Positive hemodynamic response to vasopressin after 6hours of infusion was independently associated with lower mortality in a previous retrospective study of patients with septic shock. However, factors previouslyassociated with higher plasma vasopressin concentration were not associated with response, and the relationship between plasma vasopressin concentration and hemodynamic response has not been evaluated. This cross-sectional study compared plasma vasopressin concentrations in hemodynamic responders and nonresponders tovasopressin in patients with septic shock to evaluate plasma vasopressin concentration as a therapeutic target for hemodynamic response to vasopressin. Adult patients with septic shock were included if they were treated with fixed-dose vasopressin as an adjunct to catecholamines for at least 3hours. Patients were assigned to groups based on vasopressin response. Ten hemodynamic responders to vasopressin and eight nonresponders were included. Blood samples for plasma vasopressin concentration were collected 3-6hours after vasopressin initiation. Baseline characteristics were similar between groups. No difference was detected in plasma vasopressin concentrations between hemodynamic responders and nonresponders (median 88.6pg/ml [interquartile range (IQR) 84.4-107.5pg/ml] vs 89.9pg/ml [IQR 67.5-157.4pg/ml], p=0.79, respectively). We also did not detect a difference between groups after correcting for vasopressin dose; median vasopressin plasma concentration per 0.01 units/minute of vasopressin infusion for responders was 25.9pg/ml (IQR 21.8-31.8pg/ml) versus 29.5pg/ml (IQR 23.0-57.5pg/ml, p=0.48) for nonresponders. No difference in clinical outcomes was detected between groups. The findings were robust to multiple sensitivity analyses. This study does not support the use of plasma vasopressin concentrations as a therapeutic target to predict hemodynamic response to exogenous vasopressin in septic shock.

Central Transient Receptor Potential Vanilloid 4 Contributes to Systemic Water Homeostasis through Urinary Excretion.

Intracerebroventricular (icv) injection of transient receptor potential vanilloid 4 (TRPV4) agonists 4α-phorbol-12, 13-didecanoate (4α-PDD) and GSK101690A increased urinary excretion under the physiological condition. TRPV4 antagonists ruthenium red and HC-067047 significantly blocked increased urinary volume after intragastric administration of water and 4α-PDD-induced diuresis. Administration of the TRPV4 agonists did not significantly change the plasma concentration of vasopressin or atrial natriuretic factor. Pretreatment with indomethacin inhibited the diuresis induced by 4α-PDD. Moreover, icv injection of prostaglandin (PG) F2α produced diuretic effects. These findings indicate that central TRPV4 regulates urine excretion, which contributes to systemic water homeostasis in vivo. The underlying mechanisms are suggested to involve PG synthesis, but not release of vasopressin or atrial natriuretic factor.

Acute Effects of Tolvaptan on Renal Hemodynamics in Autosomal Dominant Polycystic Kidney Disease &amp;lt;br/&amp;gt;—A Randomized, Cross-Over, Double Blind, Placebo-Controlled Study of Renal Plasma Flow and Glomerular Filtration Rate

Background: Previous studies have shown that reduced renal plasma flow (RPF) may play a role in progression of renal disease in autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan, a vasopressin 2 antagonist, reduces growth of total kidney volume and slows the decrease in estimated glomerular filtration rate (eGFR) in ADPKD. The purpose of this randomized, cross-over, double-blind, placebo-controlled study was to investigate if acute tolvaptan treatment increases RPF in ADPKD patients. Methods: Eighteen ADPKD patients (chronic kidney disease stages I-III) were investigated twice (min. 10 days apart) after acute treatment with either tolvaptan 60 mg or placebo. Two hours after treatment RPF and GFR were estimated by Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography. During the examination day, central and brachial blood pressures (BP) were measured using Mobil-O-Graph® PWA. We also measured plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin II (p-AngII) and aldosterone (p-Aldo), urine excretion of aquaporin 2 (u-AQP2), urine output (OU), urine osmolality (u-Osm) and fractional excretion of sodium (FENa). Results: 99-mTc-DTPA renography showed a similar RPF (673 ± 262 ml/min after tolvaptan vs. 650 ± 209 ml/min after placebo, p = 0.571) and GFR (78 ± 26 ml/min after tolvaptan vs. 79 ± 21 ml/min after placebo p = 0.774) after tolvaptan and placebo treatment. P-AVP and UO increased and u-Osm decreased after tolvaptan and remained unchanged during placebo. Systolic BP tended to decrease during renography during tolvaptan. Very small or insignificant changes were seen in PRC, p-AngII and p-Aldo. Conclusions: Acute tolvaptan treatment did not change renal hemodynamics in ADPKD.

Infant Birthweight and Postpartum Hypertension in African Green Monkeys

Postpartum hypertension (PPHT) is characterized by significantly elevated arterial pressure developing within 48 hours following delivery. PPHT affects 2% of all pregnancies and the etiology remains unclear. We have previously reported that the African Green Monkey (AGM; Chlorocebus aethiops sabaeus) develops gestational hypertension with pathophysiological features of preeclampsia. In this study, we report characteristics of PPHT in the AGM that occurs in the absence of hypertension before or after the onset of pregnancy. Systolic blood pressures (SBP) were collected using forearm plethysmography under ketamine sedation (15 mg/kg i.m.). Animals were characterized normotensive (NT; SBP &lt; 120 mmHg) and postpartum hypertensive (PPHT; SBP ≥ 140 mmHg developing within 48 hours following delivery). All PPHT were NT pre‐ and during pregnancy. Twenty‐four hour urine was collected in the third trimester and two weeks postpartum for three consecutive days. SBP for nonpregnant, NT was 98.7 ± 3.7 mmHg (n=18), third trimester SBP for NT was 107.0 ± 4.4 mmHg (n=5), and postpartum day 14 (PP14) SBP for NT was 94.0 ± 12.3 mmHg (n=4; p&gt;0.05). Nonpregnant SBP for PPHT was 115.8 ± 17.6 mmHg (n=8), third trimester SBP was 112.1 ± 13.3 mmHg (n=6), and PPHT, PP14 SBP was 137.2 ± 14.3 mmHg (n=6; p &lt;0.05 PP14 vs. third trimester). Nonpregnant plasma osmolality for NT was 306.3 ± 3.6 mOsm/kg (n=13) and third trimester NT plasma osmolality was 298.7 ± 4.6 mOsm/kg (n=7; p&gt;0.05). Third trimester plasma osmolality for PPHT was 288.8 ± 4.6 mOsm/kg (n=6) and 312.5 ± 5.7 mOsm/kg at PP14 (n=6; p&lt;0.05 vs. third trimester). Nonpregnant protein excretion for NT was 472.5 ± 58.0 mg/day (n=13) and 501.8 ± 104.6 mg/day in third trimester (n=5; p&gt;0.05). In PPHT animals, nonpregnant protein excretion was 684.5 ± 152.1 mg/day (n=1), 472.7 ± 62.1 mg/day in third trimester (n=6), and 171.7 ± 68.0 mg/day at PP14 (n=5; p&lt;0.05 PP14 vs. third trimester). Nonpregnant sodium excretion for NT was 2.4 ± 0.4 mmol/day (n=13) and third trimester for NT was 1.8 ± 0.6 mmol/day (n=5; p&gt;0.05). Nonpregnant sodium excretion for PPHT was 0.3 ± 1.4 mmol/day (n=1), third trimester for PPHT was 2.2 ± 0.5 mmol/day (n=6), and PP14 sodium excretion for PPHT was 3.4 ± 0.6 mmol/day (n=5; p &gt;0.05). Babies born to mothers who ultimately developed PPHT were of a higher birthweight than those born to NT mothers (NT 338.2 ± 25.5 g, n=7; PPHT 404.5 ± 14.1 g, n=6; p&lt;0.05). This data demonstrates that postpartum hypertension in the AGM is associated with decreased protein excretion, and increased SBP after delivery when compared to the third trimester of pregnancy. The mechanisms of this PPHT are largely unknown. Ongoing studies will evaluate changes in kidney function, plasma vasopressin concentrations, and plasma renin activity. The AGM has many physiological and behavioral similarities to humans, making the species an optimal model for the study of pregnancy disorders such as PPHT.Support or Funding InformationBiomedical Science Research Group, American Heart Association Predoctoral Fellowship 17PRE33670127This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Central angiotensin-(1-7) increases osmotic thirst.

What is the central question of this study? The central goal of this study was to understand the effects of central angiotensin-(1-7) on basal and osmotically stimulated water intake in rats. What is the main finding and its importance? This study demonstrated that central administration of angiotensin-(1-7) did not induce thirst in basal conditions but increased water intake after osmotic stimulation, such as water deprivation and salt loading. These results indicate a new function for this peptide, which, in turn, allows for future research on the mechanisms through which angiotensin-(1-7) influences osmotic thirst. Angiotensin-(1-7) [Ang-(1-7)] is generated by type 2 angiotensin-converting enzyme (ACE2) and binds to the MAS receptor. Although it is well known that Ang-(1-7) functionally antagonizes the effects of the classical renin-angiotensin system in several situations, the role of Ang-(1-7) in hydromineral homeostasis is not clear. The aim of this study was to assess the role of Ang-(1-7) on neuroendocrine responses to hyperosmolality in rats. Male Wistar rats were divided into the following three groups: control; 24 h of water deprivation (WD); and 24h of salt loading (SL; 1.8% NaCl). Intracerebroventricular (i.c.v.) injections of Ang-(1-7) or vehicle were given to assess water intake and plasma concentration of vasopressin. Additionally, the brains from control and WD groups were collected to evaluate gene expression in the subfornical organ (SFO), paraventricular nucleus (PVN) and supraoptic nucleus (SON). It was found that i.c.v. Ang-(1-7) did not change water and salt intake in control rats; however, Ang-(1-7) increased water intake after WD and SL, with no change in salt intake. Plasma vasopressin was not changed by i.c.v. Ang-(1-7) in control or WD rats. Moreover, WD increased Mas gene expression in the SON and PVN, with no changes in Ace2 mRNA levels. In conclusion, Ang-(1-7) increases thirst after osmotic stimuli, indicating that a previous sensitization to its action is necessary. This finding is consistent with the increased Mas gene expression in the PVN and SON after water deprivation.

Gastric myoelectrical and neurohormonal changes associated with nausea during tilt-induced syncope.

Nausea is a common prodromal symptom of neurally mediated syncope, but the biological factors linking nausea with syncope have not been studied. We aimed to characterize nausea during tilt-induced syncope by exploring related changes in gastric myoelectrical activity and plasma epinephrine, norepinephrine, and vasopressin concentrations across study phases of recumbency, tilt, syncope, and recovery. Electrogastrographic and plasma hormone changes were compared between patients with tilt-induced syncope and nausea (n=18) and control subjects (n=6) without symptoms or hemodynamic changes during tilt-table testing. Over a 4-minute period preceding syncope, sequential electrogastrography epochs demonstrated an increase over time in bradygastria (P=.003) and tachygastria (P=.014) power ratios, while the dominant frequency (P<.001) and the percent normogastria (P=.004) decreased. Syncope led to significant differences between cases and controls in electrogastrographic power ratios in each frequency range: bradygastria (P=.001), tachygastria (P=.005), and normogastria (P=.03). Nausea always followed electrogastrographic changes, and nausea resolution always preceded electrogastrographic normalization. Plasma vasopressin (676.5±122.8 vs 91.2±15.3pg/mL, P=.012) and epinephrine (434±91.3 vs 48.7±2.5pg/mL, P=.03), but not norepinephrine (P>.05), also differed with syncope between cases and controls. The nausea related to tilt-induced syncope is temporally associated with changes in gastric myoelectrical activity and increases in plasma vasopressin and epinephrine. The biological mechanisms that induce syncope are physiologically distinct from other experimental models of nausea such as illusory self-motion, yet nausea with syncope appears to have similarly associated electrogastrographic and hormone changes. Thus, tilt-induced syncope could serve as an informative experimental model for nausea research.

Dietary cation and anion difference: Effects on milk production and body fluid distribution in lactating dairy goats under tropical conditions.

This study aimed to determine the effect of dietary cation and anion difference (DCAD) on milk production and body fluid distribution in lactating dairy goats. Ten dairy goats were selected and divided into two groups, five animals each. Animals received either control DCAD (control, 22.81mEq/100g dry matter (DM)) or high DCAD (DCAD, 39.08mEq/100g DM). The results indicated that rectal temperature (Tr), respiration rate, milk yield and compositions did not differ between groups. But the percentage change of Tr from the DCAD group was lower than the control group between 09.00 and 13.00hours. DM intake tended to increase in the DCAD group. Dairy goats in the DCAD group drank more water, but urinary excretion and plasma antidiuretic hormone concentration remained unchanged. Apparent water balance was higher from the DCAD group over 24h. There was no effect of DCAD on plasma and blood volumes, but tended to increase in extracellular fluid and thereby increased total body water. The present results indicate that animals supplemented with high DCAD increase their total body water and apparent water balance. These results have contributed to the process of adaptation for evaporative cooling and would be useful in slowing down the elevation in Tr.

Effect of tolvaptan on renal handling of water and sodium, GFR and central hemodynamics in autosomal dominant polycystic kidney disease during inhibition of the nitric oxide system: a randomized, placebo-controlled, double blind, crossover study

BackgroundTolvaptan slows progression of autosomal dominant polycystic kidney disease (ADPKD) by antagonizing the vasopressin-cAMP axis. Nitric oxide (NO) stimulates natriuresis and diuresis, but its role is unknown during tolvaptan treatment in ADPKD.MethodsEighteen patients with ADPKD received tolvaptan 60 mg or placebo in a randomized, placebo-controlled, double blind, crossover study. L-NMMA (L-NG-monomethyl-arginine) was given as a bolus followed by continuous infusion during 60 min. We measured: GFR, urine output (UO), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of aquaporin-2 channels (u-AQP2) and epithelial sodium channels (u-ENaCγ), plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensinII (p-AngII), aldosterone (p-Aldo), and central blood pressure (cBP).ResultsDuring tolvaptan with NO-inhibition, a more pronounced decrease was measured in UO, CH2O (61% vs 43%) and FENa (46% vs 41%) after placebo than after tolvaptan; GFR and u-AQP2 decreased to the same extent; p-AVP increased three fold, whereas u-ENaCγ, PRC, p-AngII, and p-Aldo remained unchanged. After NO-inhibition, GFR increased after placebo and remained unchanged after tolvaptan (5% vs −6%). Central diastolic BP (CDBP) increased to a higher level after placebo than tolvaptan. Body weight fell during tolvaptan treatment.ConclusionsDuring NO inhibition, tolvaptan antagonized both the antidiuretic and the antinatriuretic effect of L-NMMA, partly via an AVP-dependent mechanism. U-AQP2 was not changed by tolvaptan, presumeably due to a counteracting effect of elevated p-AVP. The reduced GFR during tolvaptan most likely is caused by the reduction in extracellular fluid volume and blood pressure.Trial registrationClinical Trial no: NCT02527863. Registered 18 February 2015.

Studies of Vasopressin Secretion in Krushinskii–Molodkina Rats in Normal Conditions and during Convulsive Seizures

The aim of the present work was to study the secretory activity of vasopressinergic neurons in the hypothalamus in Krushinskii–Molodkina rats, which have a predisposition to audiogenic epilepsy, in normal conditions and during audiogenic convulsive seizures. Serum vasopressin and neurohypophyseal neurophysin II levels were compared in Wistar and Krushinskii–Molodkina rats. These studies demonstrated a decreased blood vasopressin level and an increased neurohypophyseal neurophysin II level in rats predisposed to audiogenic epilepsy, which is evidence for inhibition of the release of vasopressin into the blood. Analysis of vasopressin levels at different stages of convulsive seizures revealed a significant increase in the plasma vasopressin concentration at the clinic-tonic stage of convulsive seizures. Thus, this is the first study demonstrating that Krushinskii–Molodkina rats predisposed to audiogenic epilepsy have lower levels of vasopressinergic neuron secretory activity than sound-insensitive Wistar rats. A significant increase in plasma vasopressin at the clonic-tonic stage of convulsive seizures is evidence that the vasopressinergic neurosecretory system has a role in mediating audiogenic convulsive seizures.

The Resuscitative and Pharmacokinetic Effects of Humeral Intraosseous Vasopressin in a Swine Model of Ventricular Fibrillation.

Twenty-seven Yorkshire-cross swine (60 to 80 kg) were assigned randomly to three groups: HIO (n=9), IV (n=9), and a control group (n=9). Ventricular fibrillation was induced and untreated for two minutes. Chest compressions began at two minutes post-arrest and vasopressin (40 U) administered at four minutes post-arrest. Serial blood specimens were collected for four minutes, then the swine were resuscitated until ROSC or 29 post-arrest minutes elapsed. Fisher's Exact test determined ROSC was significantly higher in the HIO 5/7 (71.5%) and IV 8/11 (72.7%) groups compared to the control 0/9 (0.0%; P=.001). Odds ratios of ROSC indicated no significant difference between the treatment groups (P=.68) but significant differences between the HIO and control, and the IV and control groups (P=.03 and .01, respectively). Analysis of Variance (ANOVA) indicated the mean time to ROSC for HIO and IV was 621.20 seconds (SD=204.21 seconds) and 554.50 seconds (SD=213.96 seconds), respectively, with no significant difference between the groups (U=11; P=.22). Multivariate Analysis of Variance (MANOVA) revealed the maximum plasma concentration (Cmax) and time to maximum concentration (Tmax) of vasopressin in the HIO and IV groups was 71753.9 pg/mL (SD=26744.58 pg/mL) and 61853.7 pg/mL (SD=22745.04 pg/mL); 111.42 seconds (SD=51.3 seconds) and 114.55 seconds (SD=55.02 seconds), respectively. Repeated measures ANOVA indicated no significant difference in plasma vasopressin concentrations between the treatment groups over four minutes (P=.48). The HIO route delivered vasopressin effectively in a swine model of VF. Occurrence, time, and odds of ROSC, as well as pharmacokinetic measurements of HIO vasopressin, were comparable to IV. Burgert JM , Johnson AD , Garcia-Blanco J , Fulton LV , Loughren MJ . The resuscitative and pharmacokinetic effects of humeral intraosseous vasopressin in a swine model of ventricular fibrillation. Prehosp Disaster Med. 2017;32(3):305-310.

Comparison of different levels and lengths of restricted drinking water availability and measurement times with Katahdin sheep and Boer and Spanish goat wethers

Thirty-six yearling Boer goat (BOE), Katahdin sheep (KAT), and Spanish goat wethers (SPA) were used to study conditions for evaluating resilience to restricted drinking water availability. Moderate quality grass hay was consumed ad libitum with concentrate (80% corn, 20% soybean meal) supplemented at 0.5% BW. Baseline conditions were determined in the last 2 wk of a 3-wk period (i.e., 100% level). Thereafter, water availability was decreased by 10% every 1 (1X) or 2 wk (2X) to 40% of baseline intake (i.e., 90, 80, 70, 60, 50, and 40% levels), but also with 2 wk at 40% for the 1X restriction treatment. There was an interaction (P<0.001) between animal type (AT) and restriction level in hay DM intake, with values of 346, 360, 358, 276, 286, 235, and 176g/day for BOE, 656, 592, 592, 469, 522, 407, and 307g/day for KAT, and 392, 390, 368, 273, 298, 298, and 219g/day for SPA at levels of 100, 90, 80, 70, 60, 50, and 40%, respectively (SE=29.1). Moreover, hay DM intake by 2X wethers was much lower in wk 2 vs. 1 at the 40% level (week×level interaction, P=0.008; 409, 369, 345, 377, 336, and 276g/day in wk 1 and 428, 398, 312, 352, 310, and 203g/day in wk 2 at 90, 80, 70, 60, 50, and 40% levels, respectively; SE=23.4). Restriction level affected (P<0.001) plasma cortisol concentration in 2X wethers on the last day at each level (12.4, 14.0, 23.3, 26.4, and 32.6nmol/L for 100, 70, 60, 50, and 40% levels, respectively; SE=3.62). Plasma vasopressin concentration in 2X wethers at the end of each week at 60, 50, and 40% levels was affected by an interaction (P=0.006) between week and level (3.98, 5.61, and 7.84 for wk 1 and 6.40, 7.22, and 7.06pmol/L for wk 2, respectively; SE=0.564). In conclusion, there was some indication that DM intake by KAT was more subject to adverse effects of very low water availability but not mild restriction compared with goats. Based on vasopressin concentration, a length of at least 2 wk rather than 1 with a set level(s) of restricted water availability seems desirable, which might also increase meaningfulness of measures such as BW. Results for DM intake and cortisol concentration suggest appropriateness of a maximum restriction level of 50%.