Vasopressin Receptor Research Articles

An LC–MS/MS assay for estimating conivaptan in human plasma

AbstractWe developed and validated a liquid chromatography–mass spectrometry (LC–MS/MS) method for detecting conivaptan, an arginine vasopressin receptor blocker, in human plasma to facilitate future pharmacokinetic studies. After acetonitrile protein precipitation, analytes were separated on a Grace Alltima HP C18 reverse-phase column (5 μm, 2.1 × 50 mm), and gradient elution was performed using 0.1% formic acid and 5 mM ammonium formate in acetonitrile–water (1:9) and acetonitrile–water (9:1) over a 4-min run time. Positive-mode electrospray ionization and multiple reaction monitoring were applied. The assay was linear over the concentration range of 1–500 ng mL−1, with confirmed accuracy (intra-batch, 0.5–1.1%) and precision (intra-batch relative standard deviation [RSD], ≤5.7%; inter-batch RSD, ≤6.8%). Extraction recovery varied between 94.2–100.5%, and the matrix effect was 94.9–97.0%. To establish the stability, we examined plasma for 17 h at room temperature, 21 h at 2–8 °C, 57 days at −70 °C for three freeze-thaw cycles, and after processing for 52 h in the autosampler. We detected acceptable stability under all examined conditions. Hemolysis, hyperlipidemia, and dilution integrity satisfied the validation criteria. The method developed in this current study will help accurately quantify conivaptan in human plasma and define its clinical pharmacokinetics in the future.

A lipidated peptide derived from the C-terminal tail of the vasopressin 2 receptor shows promise as a new β-arrestin inhibitor.

β-arrestins play pivotal roles in seven transmembrane receptor (7TMR) signalling and trafficking. To study their functional role in regulating specific receptor systems, current research relies mainly on genetic tools, as few pharmacological options are available. To address this issue, we designed and synthesised a novel lipidated phosphomimetic peptide inhibitor targeting β-arrestins, called ARIP, which was developed based on the C-terminal tail (A343-S371) of the vasopressin V2 receptor. As the V2R sequence has been shown to bind β-arrestins with high affinity, we added an N-terminal palmitate residue to allow membrane tethering and cell entry. Here, using BRET2-based biosensors, we demonstrated the ability of ARIP to inhibit agonist-induced β-arrestin recruitment on a series of 7TMRs that includes both stable and transient β-arrestin binders, with efficiencies that dependent on receptor type. In addition, we showed that ARIP was unable to recruit β-arrestins to the cell membrane by itself, and that it did not interfere with G protein signalling. Molecular modelling studies also revealed that ARIP binds β-arrestins as does V2Rpp, the phosphorylated peptide derived from V2R, and that replacing the p-Ser and p-Thr residues of V2Rpp with Glu residues does not alter ARIP's inhibitory activity on β-arrestin recruitment. Importantly, ARIP exerted an opioid-sparing effect in vivo, as intrathecal injection of ARIP potentiated morphine's analgesic effect in the tail-flick test, consistent with previous findings of genetic inhibition of β-arrestins. ARIP therefore represents a promising pharmacological tool for investigating the fine-tuning roles of β-arrestins in 7TMR-driven pathophysiological processes.

Pharmacological and Interventional Approaches to Ascites Management in Cirrhosis: A Meta-Analysis

Background: Ascites, a common complication of cirrhosis, significantly impacts patient morbidity and mortality. This meta-analysis evaluated the efficacy and safety of various pharmacological and interventional approaches for ascites management in patients with cirrhosis. Methods: A systematic search of PubMed, Embase, and Cochrane Library databases was conducted from January 2013 to December 2024, identifying randomized controlled trials (RCTs) comparing different pharmacological agents (diuretics, albumin, vasopressin receptor antagonists) and interventional procedures (large-volume paracentesis, transjugular intrahepatic portosystemic shunt [TIPS]) in cirrhotic patients with ascites. The primary outcome was complete ascites resolution. Secondary outcomes included time to ascites recurrence, adverse events, and mortality. A random-effects model was used to pool data, and heterogeneity was assessed using the I² statistic. Results: Twelve RCTs (n=2848 patients) met the inclusion criteria. Diuretics plus albumin was superior to diuretics alone in achieving complete ascites resolution (OR 2.18, 95% CI 1.65-2.88, p<0.001; I²=38%). Vasopressin receptor antagonists were comparable to diuretics plus albumin in terms of ascites resolution (OR 1.09, 95% CI 0.88-1.35, p=0.42; I²=12%) but associated with a lower incidence of hyponatremia (OR 0.52, 95% CI 0.35-0.78, p=0.002; I²=23%). Large-volume paracentesis was more effective than repeated small-volume paracentesis for ascites control (OR 1.75, 95% CI 1.31-2.34, p<0.001; I²=41%). TIPS was associated with a higher rate of complete ascites resolution compared to large-volume paracentesis (OR 2.45, 95% CI 1.78-3.38, p<0001; I²=35%) but a higher risk of hepatic encephalopathy (OR 2.21, 95% CI 1.48-3.30, p<0.001; I²=15%). Albumin reduced mortality in patients undergoing large-volume paracentesis (OR 0.68, 95% CI 0.49-0.94, p=0.02; I²=0%). Conclusion: This meta-analysis supports the use of diuretics plus albumin, vasopressin receptor antagonists, large-volume paracentesis, and TIPS for ascites management in cirrhosis, with the choice of therapy individualized based on patient characteristics, ascites severity, and the risk of complications.

Importance of early use of tolvaptan in hyponatremic acutely decompensated heart failure patients, a retrospective study

BackgroundHyponatremia is one of the complicating findings in acute decompensated heart failure. Decrease in cardiac output and systemic blood pressure triggers activation of renin–angiotensin–aldosterone system, antidiuretic hormone, and norepinephrine due to the perceived hypovolemia. Fluid-overloaded heart failure patients are commonly treated with loop diuretics, acutely decompensated heart failure patients tend to be less responsive to conventional oral doses of a loop diuretic, while other different diuretics could work in different part of nephron circulation system. In this study, we aim to further examine the role of tolvaptan, a vasopressin receptor antagonist, in the treatment of hyponatremia secondary to acutely decompensated heart failure.ResultsA total of 71 patients with hyponatremia secondary to ADHF were included, and all patients were given tolvaptan. 37 patients were administered tolvaptan early (up until 5 th day of admission). 34 patients received tolvaptan after 5 th day of admission mean administration as 6.86 th day, and median administration was 5 th day. Analysis showed lower length of stay in patients receiving early administration of tolvaptan compared to late administration (8.86 ± 5.06 vs 18.5 ± 9.05 p0.001, respectively). Patients with early initiation of tolvaptan also achieved a larger net increase in sodium levels at discharge compared to admission (6.46 ± 6.69 vs 3.68 ± 4.70 p0.048, respectively).ConclusionsEarly administration of tolvaptan in treating hyponatremia in acutely decompensated heart failure patients is associated with a lower length of hospitalization and a higher increase in serum sodium of patients in hyponatremic ADHF patients.

Innovations in Targeting the V2 Receptor.

Innovations in Targeting the V2 Receptor.

Aquaporin-2 in the early stages of the adenine-induced chronic kidney disease model.

Chronic kidney disease (CKD) is one of the leading health problems in the world. It is silent in the early stages and gradually progresses, inducing renal physiological and structural alterations. Moreover, CKD is associated with impaired life quality, increased risk for cardiovascular diseases, and reduced life expectancy. Different CKD animal models differ in underlying etiology, time of onset, and associated diseases. The 0.25% adenine diet induces progressive kidney damage, constituting an adequate model mimicking human CKD. Vasopressin (VP) was postulated as a mediator of CKD, mainly acting through its V2 receptors. However, the molecular mechanisms involved in the pathogenesis of this condition and its progression still are not entirely understood. This study aimed to evaluate if AQP2 expression is altered in an adenine-induced model of CKD in rats at early stages of development (two weeks) and to assess a potential beneficial effect of Tolvaptan (a V2 receptor antagonist) treatment. We showed an increased renal medullary AQP2 expression at two weeks of adenine administration. This increase was mainly cytoplasmic, explaining the increased urinary volume of CKD rats and suggesting a possible non-canonical role for AQP2. In addition, Tolvaptan effectively inhibited the V2 receptor in both control and CKD rats, decreasing AQP2 expression and increasing diuresis. Moreover, Tolvaptan slightly reduced BUN and plasma creatinine. On the other hand, the renal alterations induced by adenine in CKD rats were not prevented by Tolvaptan.

Nephrogenic diabetes insipidus: potential treatments and their mechanisms of action.

Nephrogenic diabetes insipidus (NDI) is a rare disease caused by the complete or partial resistance of the kidneys to antidiuretic hormone (ADH). NDI associated with excessive urine production and severe thirst. There are two types of NDI; acquired NDI and congenital NDI. Acquired NDI is the most common type among adults, with several factors that can cause acquired NDI, for instance, lithium therapy and electrical disorders. Congenital NDI can occur due to mutations in either the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin-2 (AQP2) gene. New effective treatments for NDI are required because the disease can be life treating if left untreated. Current animal studies showed that rolipram and metformin are two potential treatments for congenital NDI by upregulation the apical expression of AQP2 channels. Other animal studies illustrated that the combination of different drugs, such as, secretin agonist and fluvastatin could be an effective method to treat XNDI. Furthermore, some agents were found to be able to treat more than one type of NDI, for example, sildenafil citrate could be potently used to treat acquired NDI and XNDI, while statins could be promising treatments for congenital NDI and autosomal NDI. However, further investigation and human trials are needed before it can be decided if these drugs can be clinically used as a treatment for NDI.

Role of Desmopressin in Bleeding Disorders: What Indian Physicians Need to Know?

Desmopressin (1-deamino-8-D-arginine vasopressin), formerly introduced for the treatment of diabetes insipidus, is a well-known analog of vasopressin, that is, antidiuretic hormone (ADH). Subsequently, after the late 1970s, it has emerged as the medication of choice for type 1 von Willebrand's disease (vWD) and minor hemophilia A. Prothrombotic factors FVIII and von Willebrand factor (vWF) are released from storage sites when vasopressin receptors are targeted by desmopressin. It also facilitates platelet-vessel wall adhesion, resulting in a substantial hemostatic effect. Research studies have shown that desmopressin administration can lead to up to a fourfold increase in vWF levels, highlighting its hemostatic actions. Desmopressin is commonly used in conditions like nocturnal polyuria leading to nocturia or nocturnal enuresis, diabetes insipidus, von Willebrand disease, uremic bleeding, and hemophilia A. Desmopressin is also used to avoid rapid sodium correction along with hypertonic saline, management of intracranial bleed due to the use of antiplatelet agents, and trauma resuscitation with active hemorrhage. It is also used in bleeding disorders, dental extractions, epistaxis, and menstrual bleeding. Hence, it is imperative that clinicians become acquainted with the use of desmopressin, which has become a common medication for many patients with congenital bleeding disorders. Desmopressin is included in the treatment guidelines for vWD.

Diuretic Potentiation Strategies in AcuteHeartFailure.

Several trials have evaluated diuretic-based strategies to improve symptoms and outcomes in patients with acute heart failure (AHF). The authors sought to summarize the effect of different combination strategies on symptoms, physical signs, physiological variables, and outcomes in patients with AHF. Twelve trials were identified that assessed the addition of thiazide diuretics, sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, vasopressin receptor antagonists, carbonic anhydrase inhibitors, or loop diuretic intensification to conventional therapy for AHF. The trials evaluated short-term markers of congestion and symptoms, and none were powered for clinical outcomes. Short-term responses (such as relief from dyspnea, physical signs of congestion, and weight change) varied greatly across studies; all diuretic strategies were accompanied by short-term increases in serum creatinine and did not demonstrate benefits on mortality or recurrent heart failure events. The available evidence suggests that intensification of loop diuretic agents produces relief of physical signs of decongestion, but the importance of different strategies for short-term decongestion strategy for health status and long-term outcomes has not been established.

Hyponatremia in Neurosurgical Patients

Hyponatremia refers to a common and potentially dangerous electrolyte imbalance observed in neurosurgical patients, particularly following traumatic brain injuries, subarachnoid hemorrhages, brain tumors, and pituitary surgeries. The paper discusses primary causes and pathophysiology of hyponatremia, including the syndrome of inappropriate secretion of antidiuretic hormone, central adrenal insufficiency, and cerebral salt wasting syndrome. The paper presents differential diagnostic approaches for accurately identifying the underlying causes of hyponatremia, as well as therapeutic strategies that include hypertonic sodium solution infusions, hydrocortisone replacement therapy, and the use of vasopressin receptor antagonists. The study delineates the potential complications associated with overly rapid correction of sodium levels, such as osmotic demyelination syndrome. It emphasizes the importance of accurate diagnosis and timely treatment to enhance patient outcomes and minimize the risk of complications.

Can the Bladder Itself "Measure" Volume, and Thereby Help to Determine When Initiation of Voiding Should Occur? ICI-RS 2024.

To answer the question of whether the bladder itself can to any extent control or modulate the initiation of voiding. This subject was discussed at the International Consultation on Incontinence-Research Society (ICI-RS) 2024 conference in Bristol, UK in a proposal session. Cells in the bladder wall sense the local environment via a diverse array of ion channels and receptors which together provide input to motor-sensory and signal transduction mechanisms. A purinergic signal transduction system provides a high-gain mucosal chemosensitive transduction pathway between bladder wall stretch during filling and graded afferent activation. Recent studies established cross-species similarities in the regulation of urine storage which include the upregulation of aquaporin (water) channels during bladder filling/wall stretch, in the bladder. In addition to the endocrine hypothalamus/pituitary axis production, urothelial production of arginine vasopressin acts on urothelial vasopressin receptors in a paracrine manner causing aquaporin channel upregulation, reducing the bladder volume and delaying sensation of fullness. Bladder shape influences the sensory systems involved in the perception of bladder volume; moreover irregular bladder shapes may correlate with overactive bladder. Volume measuring and signaling threshold-determining mechanisms in the bladder along with shape and permeability act to influence the timing and type of signaling to the CNS; although this is not always followed by a consecutive action. The hierarchical grading of the signals originating from the bladder among other peripheral bodily or central signals are crucial factors that determine whether the bladder is "allowed" to initiate voiding.

Molecular Interaction Between Vasopressin and Insulin in Regulation of Metabolism: Impact on Cardiovascular and Metabolic Diseases.

Numerous compounds involved in the regulation of the cardiovascular system are also engaged in the control of metabolism. This review gives a survey of literature showing that arginine vasopressin (AVP), which is an effective cardiovascular peptide, exerts several direct and indirect metabolic effects and may play the role of the link adjusting blood supply to metabolism of tissues. Secretion of AVP and activation of AVP receptors are regulated by changes in blood pressure and body fluid osmolality, hypoxia, hyperglycemia, oxidative stress, inflammation, and several metabolic hormones; moreover, AVP turnover is regulated by insulin. Acting on V1a receptors in the liver, AVP stimulates glycogenolysis, reduces synthesis of glycogen, and promotes fatty acid synthesis and acetyl CoA carboxylase activity. Stimulating V1b receptors in the pancreatic islands, AVP promotes release of insulin and glucagon-like peptide-1 (GLP-1) and potentiates stimulatory effects of glucose and ACTH on secretion of insulin. Simultaneously, insulin increases AVP secretion by neurons of the paraventricular nucleus and the supraoptic nucleus. There is strong evidence that secretion of AVP and its metabolic effectiveness are significantly altered in metabolic and cardiovascular diseases. Both experimental and clinical data indicate that inappropriate interactions of AVP and insulin play an important role in the development of insulin resistance in obesity and diabetes mellitus.

Nephrogenic diabetes insipidus results from a novel in-frame deletion of AVPR2 gene in monozygotic-twin boys and their mother and grandmother.

Mutations in the AVPR2 gene are the most common cause of nephrogenic diabetes insipidus(NDI). In-frame deletions of the AVPR2 gene are a rare variant that results in NDI. We report a novel variant of the p.H138del in an NDI family with twin male patients and three female carriers of different clinical phenotypes. The proband's blood genome was sequenced witha panel, and the variants were classified according to ACMG/AMP (2015) guidelines. X chromosome inactivation (XCI) was analyzed in the peripheral blood of his mother, grandmother, and maternal aunt, respectively. The haplotypes of the X chromosome were determined using their STR loci. A novel in-frame deletion in the AVPR2 gene was detected in monozygotic-twin boys, and his mother, grandmother, and maternal aunt were heterozygous carriers. The two boys showed typical NDI, and their mother and grandmother presented polydipsia, polydipsia, and polyuria, but the maternal aunt did not have similar symptoms. The blood XCI results of the mother, grandmother, and maternal aunt showed random inactivation (36.18 , 48.37, and 49.30 %, respectively). The X haplotype indicated that the variant of the mother and grandmother was on their activated X chromosomes(Xa), while the maternal aunt's variant was on her inactivated X chromosome(Xi). In-frame deletion of the AVPR2 gene within its functional domain can significantly affect protein function, which is one of the vital causes of NDI. The clinical variability of female carriers of AVPR2 is associated with underlying environmental and epigenetic factors or complex recombination of the X chromosomes.

The glycoprotein hormone receptor (LGR1) influences Malpighian tubule secretion rate in Rhodnius prolixus.

In the hemipteran Rhodnius prolixus, successful post-prandial diuresis is accomplished through the synergistic actions of the peptidergic diuretic hormone RhoprCRF/DH and the biogenic amine 5-hydroxytryptamine (5-HT), and by an antidiuretic hormone RhoprCAPA-2 that terminates diuresis by inhibiting this synergy. Lateral neurosecretory cells (NSCs) in the mesothoracic ganglionic mass release RhoprCRF/DH, while midline NSCs release RhoprCAPA-2 during blood feeding. These NSCs co-express GPA2/GPB5, a conserved glycoprotein hormone involved in various physiological processes across bilaterians. This study investigated the influence of GPA2/GPB5 signaling on Malpighian tubule (MT) fluid secretion in R. prolixus. GPB5-like immunoreactivity in lateral and midline NSCs decreased following a blood meal, suggesting release and a role in diuresis. Downregulating the GPA2/GPB5 receptor LGR1 via RNA interference resulted in an increased basal fluid secretion rate in MTs, which was inhibited by the antidiuretic hormone RhoprCAPA-2. dsLGR1 treatment reduced the effects of RhoprCRF/DH and 5-HT on MT secretion and eliminated their synergism. RT-qPCR revealed that the expression of the diuretic and antidiuretic hormone receptors decreased in MTs of dsLGR1-injected insects, indicating that GPA2/GPB5 influences the expression of these other receptors. Downregulating LGR1 resulted in a smaller blood meal size and disrupted the normal time course of diuresis. As LGR1 is the most abundantly expressed G protein-coupled receptor gene in R. prolixus MTs, our results suggest that GPA2/GPB5 signaling has a critical role in regulating the timing and success of water retention in the unfed state, and in the complex processes associated with feeding and diuresis in R. prolixus.

The natural history of untreated X-linked nephrogenic diabetes insipidus with mutation in the vasopressin V2 receptor gene.

Nephrogenic diabetes insipidus (NDI) results from the kidneys' inability to concentrate urine. We describe a 6-month-old male with a history of poor weight gain who presented with an incidental finding of hypernatremia (155mEq/L) during an episode of acute gastroenteritis. The arginine vasopressin (AVP) test, along with molecular analysis revealing the M272R mutation in the AVP receptor 2 (AVPR2) gene, confirmed the diagnosis of congenital NDI. Interestingly, this mutation was also identified in the patient's maternal grandfather, who had never been diagnosed or treated for NDI despite a history of polydipsia, polyuria, and evidence of chronic kidney disease (CKD), severe bilateral hydronephrosis, hypertension, and severe bladder dysfunction. Early intervention with hydrochlorothiazide in the infant resulted in a significant reduction in urinary output and improved growth. The untreated grandfather's case highlights the potential severity of untreated NDI and the benefits of timely therapeutic intervention. This report contributes to the limited long-term data on congenital NDI, emphasizing the critical role of early detection and consistent management in preventing severe complications such as CKD, hydronephrosis, and bladder dysfunction. Regular follow-up, including renal ultrasound and monitoring of renal function, is essential for effectively managing NDI and improving patient outcomes.

Tolvaptan for Euvolemic and Hypervolemic Hyponatremia: A Narrative Review

Hyponatremia is an electrolyte imbalance disorder commonly found in clinical practice. Hyponatremia is associated with significant mortality and morbidity. Tolvaptan is an orally administered V2 receptor antagonist drug capable of aquaresis without excreting electrolytes, thus increasing plasma sodium concentration. Results from clinical trials showed tolvaptan to be a relatively safe and effective treatment in euvolemia and hypervolemia hyponatremia.

Angiotensin 1-7 injected into the rat paraventricular nucleus of hypothalamus increases blood pressure and heart rate via various receptors.

Although angiotensin 1-7 (Ang 1-7) and its role as a part of the "protective" axis of the renin-angiotensin system are well described in the literature, the mechanisms of its angiotensin II-like pressor and tachycardic effects following its acute central administration are not fully understood. It was the aim of the present study to examine which receptors contribute to the aforementioned cardiovascular effects. Ang 1-7 and antagonists for glutamate, GABA, vasopressin, thromboxane A2 (TP), α1-adrenergic, and P2X purinoceptors or modulators of oxidative stress were injected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anesthetized male Wistar rats. Acute injection of Ang 1-7 into the PVN increased blood pressure (BP) by about 15 mmHg and heart rate (HR) by about 14 beats/min. After preinjection with bicuculline (GABAA receptor antagonist), CNQX + D-AP5 (AMPA/kainate and NMDA receptor antagonists) and SQ29548 (TP receptor antagonist) the BP and HR reactions to Ang 1-7 were attenuated or abolished. The vasopressin V1A and V1B receptor antagonists conivaptan and nelivaptan, and the NADPH oxidase inhibitor apocynin even reversed the pressor and tachycardic effects of Ang 1-7. Antagonists of P2X (PPADS) and α1-adrenergic receptors (prazosin), the free radical scavenger tempol and the superoxide dismutase inhibitor DETC did not modify the cardiovascular effects of Ang 1-7. The (Mas receptor-related) rise in BP and HR evoked by Ang 1-7 administered to the rat PVN is linked to glutamate, vasopressin, GABAA and thromboxane receptors, and to oxidative stress, but does not seem to involve α1-adrenergic or P2X receptors.

Intestinal butyric acid-mediated disruption of gut hormone secretion and lipid metabolism in vasopressin receptor-deficient mice.

Arginine vasopressin (AVP), known as an antidiuretic hormone, is also crucial in metabolic homeostasis. Although AVP receptor-deficient mice exhibit various abnormalities in glucose and lipid metabolism, the mechanism underlying these symptoms remains unclear. This study aimed to explore the involvement of the gut hormones including glucagon-like peptide-1 (GLP-1) and microbiota as essential mediators. We used the mouse GLP-1-secreting cell line, GLUTag, and performed live cell imaging to examine the contribution of V1a and V1b vasopressin receptors (V1aR and V1bR, respectively) to GLP-1 secretion. We next investigated the hormone dynamics of V1aR-deficient mice (V1aR-/- mice), V1bR-deficient mice (V1bR-/- mice), and V1aR/V1bR-double deficient mice (V1aR-/-V1bR-/-mice). AVP induced the increase in intracellular Ca2+ levels and GLP-1 secretion from GLUTag cells in a V1aR and V1bR-dependent manner. AVP receptor-deficient mice, particularly V1aR-/-V1bR-/- mice, demonstrated impaired secretion of GLP-1 and peptide YY secreted by enteroendocrine L cells. V1aR-/-V1bR-/-mice also exhibited abnormal lipid accumulation in the brown adipose tissue and skeletal muscle. We discovered that V1aR-/-V1bR-/- mice showed increased Paneth cell-related gene expression in the small intestine, which was attributed to increased fecal butyric acid levels. Exposure to butyric acid reduced GLP-1 secretion in L cell line. Additionally, human Paneth cell-related gene expressions negatively correlated with that of V1 receptor genes. The deficiency in V1 receptor genes may increase gut butyric acid levels and impair the function of L cells, thus dysregulating lipid homeostasis in the brown adipose tissue and skeletal muscle. This study highlights the importance of appropriate control of the gut microbiota and its metabolites, including butyric acid, for the optimum functioning of enteroendocrine cells.

Development of dual V1a/V2 antagonists containing triazolobenzazepine scaffold

The development of a dual V1a/V2 antagonist compound is a complex and challenging task. Conivaptan is up to now the only known V1a/V2 antagonist which was approved for the treatment of euvolemic hyponatremia. Previously, we reported RGH-122, a novel selective V1a antagonist compound. Herein, we describe several promising dual antagonist compounds, which are derived from RGH-122 by using modifications in its tail region. These modifications can result in excellent binding affinity on both V1a and V2 receptors.

Efficacy of Tolvaptan in Older Adults Undergoing Cardiac Surgery: A Single-Center Retrospective Analysis.

Globally, cardiovascular diseases remain a predominant cause of mortality. Effective fluid management is particularly critical in older adults undergoing cardiac surgery, due to their heightened risk of postoperative complications. Tolvaptan, an oral vasopressin V2 receptor antagonist, has emerged as a promising agent for fluid regulation in cardiac patients. However, its efficacy in the elderly undergoing cardiac surgery is not thoroughly evaluated. This single-center retrospective analysis included 146 older adults (≥ 65 years) who underwent cardiac surgery between January 2018 and December 2022. Patients were categorized into two groups: those receiving tolvaptan and a control group receiving traditional diuretics post-surgery. We assessed several outcomes, including hospital length of stay, 30-day mortality, postoperative renal function, and complications. The study found a significantly reduced hospitalization duration in the tolvaptan group (P=0.044), with no escalation in adverse events. The tolvaptan cohort exhibited a considerable increase in urine output on the postoperative day (POD) three (P=0.003), indicating enhanced renal function and fluid management. Serum creatinine levels notably declined by POD3 (P=0.012), and blood urea nitrogen levels were appreciably lower by POD5 (P<0.001) in the tolvaptan group. Furthermore, serum sodium levels significantly escalated on POD3 and POD5 (P<0.01) in this group, while serum potassium levels remained unchanged. Tolvaptan significantly optimizes postoperative fluid management in older adults undergoing cardiac surgery. Its administration is linked to improved renal function and a shortened hospital stay, without amplifying adverse effects. These insights could enhance clinical practices and facilitate the management of fluid overload in this vulnerable demographic.