Lifelong LUTS: Understanding the bladder's role and implications across transition phases, a comprehensive review.

INTRODUCTION: Lower urinary tract symptoms (LUTSs) are a diverse array of urinary and pelvic dysfunctions that can emerge from childhood, extend through adulthood, and persist into older age. This narrative review aims to provide a comprehensive perspective on the continuum of LUTS and shed light on the underlying mechanisms and clinical implications that span across the lower urinary tract. METHODS: A panel of five experts from Belgium, the Netherlands, India, Denmark, and the United States participated in an intensive research to explore and pinpoint existing insights into the lifelong concept of LUTS, particularly at the pelvic level. The experts reviewed the existing literature and held a webinar to discuss their findings. RESULTS: Childhood LUTS can persist, resolve, or progress into bladder underactivity, dysfunctional voiding, or pain syndromes. The Lifelong character can be explained by pelvic organ cross-talk facilitated through complex neurological and nonneurological interactions. At the molecular level, the role of vasopressin receptors in the bladder's modulation and their potential relevance to therapeutic strategies for LUTS are explored. Frailty emerges as a parallel concept to lifelong LUTS, with a complex and synergistic relationship. Frailty, not solely an age-related condition, accentuates LUTS severity with insufficient evidence regarding the effectiveness and safety profile of the available therapeutic modalities. CONCLUSION: Understanding lifelong LUTSs offers insights into genetic, anatomical, neurological, and molecular mechanisms. Further research could identify predictive biomarkers, elucidate the role of clinically translatable elements in pelvic cross-talk, and uncover molecular signatures for personalized management.

The Role of Arginine-Vasopressin in Stroke and the Potential Use of Arginine-Vasopressin Type 1 Receptor Antagonists in Stroke Therapy: A Narrative Review.

Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment strategies, particularly non-invasive interventions, are limited, thus urging the need for novel therapeutical targets. Arginine vasopressin (AVP) receptor antagonists are emerging as potential targets to treat edema formation and subsequent elevation in intracranial pressure, both significant causes of mortality in acute stroke. Here, we summarize the current knowledge on the mechanisms leading to AVP hyperexcretion in acute stroke and the subsequent secondary neuropathological responses. Furthermore, we discuss the work supporting the predictive value of measuring copeptin, a surrogate marker of AVP in stroke patients, followed by a review of the experimental evidence suggesting AVP receptor antagonists in stroke therapy. As we highlight throughout the narrative, critical gaps in the literature exist and indicate the need for further research to understand better AVP mechanisms in stroke. Likewise, there are advantages and limitations in using copeptin as a prognostic tool, and the translation of findings from experimental animal models to clinical settings has its challenges. Still, monitoring AVP levels and using AVP receptor antagonists as an add-on therapeutic intervention are potential promises in clinical applications to alleviate stroke neurological consequences.

Vasopressin and Its Analogues: From Natural Hormones to Multitasking Peptides.

Human neurohormone vasopressin (AVP) is synthesized in overlapping regions in the hypothalamus. It is mainly known for its vasoconstricting abilities, and it is responsible for the regulation of plasma osmolality by maintaining fluid homeostasis. Over years, many attempts have been made to modify this hormone and find AVP analogues with different pharmacological profiles that could overcome its limitations. Non-peptide AVP analogues with low molecular weight presented good affinity to AVP receptors. Natural peptide counterparts, found in animals, are successfully applied as therapeutics; for instance, lypressin used in treatment of diabetes insipidus. Synthetic peptide analogues compensate for the shortcomings of AVP. Desmopressin is more resistant to proteolysis and presents mainly antidiuretic effects, while terlipressin is a long-acting AVP analogue and a drug recommended in the treatment of varicose bleeding in patients with liver cirrhosis. Recently published results on diverse applications of AVP analogues in medicinal practice, including potential lypressin, terlipressin and ornipressin in the treatment of SARS-CoV-2, are discussed.

V1b vasopressin receptor trafficking and signaling: Role of arrestins, G proteins and Src kinase.

The signaling pathway of G protein-coupled receptors is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved in the vasopressin receptor V1b subtype (V1b R) trafficking and its impact on receptor signaling and regulation. For this purpose, we investigated the role of ß-arrestins in receptor desensitization, internalization and recycling and attempted to dissect the V1b R-mediated MAP kinase pathway. Using MEF cells Knocked-out for ß-arrestins 1 and 2, we demonstrated that both ß-arrestins 1 and 2 play a fundamental role in internalization and recycling of V1b R with a rapid and transient V1b R-ß-arrestin interaction in contrast to a slow and long-lasting ß-arrestin recruitment of the V2 vasopressin receptor subtype (V2 R). Using V1b R-V2 R chimeras and V1b R C-terminus truncations, we demonstrated the critical role of the V1b R C-terminus in its interaction with ß-arrestins thereby regulating the receptor internalization and recycling kinetics in a phosphorylation-independent manner. In parallel, V1b R MAP kinase activation was dependent on arrestins and Src-kinase but independent on G proteins. Interestingly, Src interacted with hV1b R at basal state and dissociated when receptor internalization occurred. Altogether, our data describe for the first time the trafficking profile and MAP kinase pathway of V1b R involving both arrestins and Src kinase family.

Dysregulation of the Renin-Angiotensin System and the Vasopressinergic System Interactions in Cardiovascular Disorders.

PURPOSE OF REVIEW: In many instances, the renin-angiotensin system (RAS) and the vasopressinergic system (VPS) are jointly activated by the same stimuli and engaged in the regulation of the same processes. RECENT FINDINGS: Angiotensin II (Ang II) and arginine vasopressin (AVP), which are the main active compounds of the RAS and the VPS, interact at several levels. Firstly, Ang II, acting on AT1 receptors (AT1R), plays a significant role in the release of AVP from vasopressinergic neurons and AVP, stimulating V1a receptors (V1aR), regulates the release of renin in the kidney. Secondly, Ang II and AVP, acting on AT1R and V1aR, respectively, exert vasoconstriction, increase cardiac contractility, stimulate the sympathoadrenal system, and elevate blood pressure. At the same time, they act antagonistically in the regulation of blood pressure by baroreflex. Thirdly, the cooperative action of Ang II acting on AT1R and AVP stimulating both V1aR and V2 receptors in the kidney is necessary for the appropriate regulation of renal blood flow and the efficient resorption of sodium and water. Furthermore, both peptides enhance the release of aldosterone and potentiate its action in the renal tubules. In this review, we (1) point attention to the role of the cooperative action of Ang II and AVP for the regulation of blood pressure and the water-electrolyte balance under physiological conditions, (2) present the subcellular mechanisms underlying interactions of these two peptides, and (3) provide evidence that dysregulation of the cooperative action of Ang II and AVP significantly contributes to the development of disturbances in the regulation of blood pressure and the water-electrolyte balance in cardiovascular diseases.

Neuroanatomical distribution and function of the vasopressin V1B receptor in the rat brain deciphered using specific fluorescent ligands.

It is now accepted that vasopressin, through V1A/V1B receptors, centrally regulates cognitive functions such as memory, affiliation, stress, fear and depression. However, the respective roles of these receptor isoforms and their contribution to stress-related pathologies remain uncertain. The development of new therapeutic treatments requires a precise knowledge of the distribution of these receptors within the brain, which has been so far hampered by the lack of selective V1B markers. In the present study, we have determined the pharmacological properties of three new potent rat V1B fluorescent ligands and demonstrated that they constitute valuable tools for simultaneous visualization and activation of native V1B receptors in living rat brain tissue. Thus, d[Leu4,Lys-Alexa 647)8]VP (analogue 3), the compound with the best affinity-selectivity/fluorescence ratio for the V1B receptor emerged as the most promising. The rat brain regions most concerned by stress such as hippocampus, olfactory bulbs, cortex and amygdala display the highest V1B fluorescent labelling with analogue 3. In the hippocampus CA2, V1B receptors are located on glutamatergic, not GABAergic neurones, and are absent from astrocytes. Using AVP-EGFP rats, we demonstrate the presence of V1B autoreceptors on AVP-secreting neurones not only in the hypothalamus, but also sparsely in the hippocampus. Finally, using both electrophysiology and visualization of ERK phosphorylation, we show analogue 3-induced activation of the V1B receptor in situ. This will help to analyse expression and functionality of V1B receptors in the brain and contribute to further explore the AVPergic circuitry in normal and pathological conditions.

Vasopressin: physiology, assessment and osmosensation.

Vasopressin (AVP) plays a major role in the regulation of water and sodium homeostasis by its antidiuretic action on the kidney, mediated by V2 receptors. AVP secretion is stimulated by a rise in plasma osmolality, a decline in blood volume or stress. V1a receptors are expressed in vascular smooth muscle cells, but the role of vasopressin in blood pressure regulation is still a matter of debate. AVP may also play a role in some metabolic pathways, including gluconeogenesis, through its action on V1a receptors expressed in the liver. It is now understood that thirst and arginine vasopressin (AVP) release are regulated not only by the classical homeostatic, intero-sensory plasma osmolality negative feedback, but also by novel, extero-sensory, anticipatory signals. AVP measurement is time-consuming, and AVP level in the blood in the physiological range is often below the detection limit of the assays. Recently, an immunoassay has been developed for the measurement of copeptin, a fragment of the pre-provasopressin molecule that is easier to measure. It has been shown to be a good surrogate marker of AVP.

Vasopressin and metabolic disorders: translation from experimental models to clinical use.

Vasopressin has many physiological actions in addition to its well-defined role in the control of fluid homeostasis and urine concentration. An increasing body of evidence suggests that the vasopressin-hydration axis plays a role in glucose homeostasis. This review summarizes the knowledge accumulated over the last decades about the influence of vasopressin in the short-term regulation of glycaemia. It describes the possible role of this hormone through activation of V1a and V1b receptors on liver and pancreas functions and on the hypothalamic-pituitary-adrenal axis. Moreover, we report recent in vivo studies demonstrating the role of vasopressin in the long-term regulation of glycaemia. Indeed, V1a- or double-V1aV1b-receptor knockout mice display significant changes in the glucose and lipid metabolism. In rats, sustained high V1aR activation increases basal glycaemia and aggravates glucose intolerance in obese rats. Finally, the translation from animal findings to human was evidenced by epidemiological and genetic studies that showed that high vasopressin level is a risk factor for hyperglycaemia, metabolic disorders and diabetes.

Terlipressin, a vasoactive prodrug recommended in hepatorenal syndrome, is an agonist of human V1, V2 and V1B receptors: Implications for its safety profile.

Terlipressin is recommended as a gold standard to treat hepatorenal syndrome complicating liver cirrhosis. It is presented as a specific V1A receptor agonist, beyond its enzymatic conversion into lysine8-Vasopressin (LVP), able to counteract the splanchnic vasodilation. However, the complete pharmacological characterization of this drug with respect to the different vasopressin receptor subtypes is missing. We studied terlipressin intrinsic properties, focusing not only on V1A, but also on other vasopressin receptor subtypes. The experimental studies were conducted on rat and human cellular models. Binding experiments were performed on rat liver membranes and CHO cells transfected with the different human vasopressin receptor subtypes. Agonist status was assessed from inositol phosphate or cyclic AMP assays, and measurement of intracellular calcium variations, performed on cultured vascular smooth muscle cells from rat aorta and human uterine artery and CHO cells. Terlipressin binds to the rat and human V1A receptors with an affinity in the micromolar range, a value 120 fold lower than that of LVP. It induces a rapid and transient intracellular calcium increase, a robust stimulation of phospholipase C but with reduced maximal efficiencies as compared to LVP, indicating a partial V1A agonist property. In addition, terlipressin is also a full agonist of human V2 and V1B receptors, with also a micromomolar affinity. CONCLUSIONS: Terlipressin is a non-selective vasopressin analogue, exhibiting intrinsic agonist properties. Its full V2 receptor agonism may result in renal effects potentially aggravating water retention and hyponatremia of cirrhosis.

Effects of Selective Agonists of V1a, V2, and V1b Receptors on Sodium Transport in Rat Kidney.

The role of subtypes of vasopressin receptors in modulation of renal sodium reabsorption was studied in in vivo experiments on Wistar rats. Selective V1a receptor agonist reduced sodium reabsorption in the kidneys and expression of these receptors increased by practically 100 times. This effect was similar to the effect of furosemide. Selective V2 receptor agonist enhanced sodium reabsorption in the kidney and simultaneously increased reabsorption of solute-free water. Stimulation of V1b receptors did not affect sodium transport. Our findings attest to the key role of V1a receptors in the regulation of renal excretion of sodium ions.

Desmopressin enhances random-pattern skin flap survival in rats: Possible role of vasopressin Type-1a and 2 receptors.

BACKGROUND: Many drugs have been explored for their role in improving skin flap survival. 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) is a synthesized form of anti-diuretic hormone (ADH) and a selective agonist for vasopressin type-2 receptors (V2 receptors). Desmopressin has been shown to improve endothelial function, induce vasodilation, and reduce inflammation. We aimed to evaluate its efficacy in enhancing flap survival and assess the role of vasopressin receptors in this process. MATERIALS AND METHODS: We randomly assigned six male Wistar rats to each study group. Different doses of desmopressin were injected intraperitoneally to find the most effective amount (8 µg/rat). SR-49059, a selective V1a receptor antagonist, was given at 2µg/rat before providing the most effective dose of desmopressin (8µg/rat). Histopathological assessments, quantitative measurements of interleukin-1ß (IL-1ß), Tumor necrosis factor-alpha (TNF-α), and Nuclear Factor-κB (NF-κB), optical imaging, and measurement of the expression levels of V2 receptor in the rat skin tissue were performed. RESULTS: Desmopressin (8µg/rat) significantly reduced the mean percentage of necrotic area compared to the control group (19.35% vs 73.57%). Histopathological evaluations revealed a notable reduction in tissue inflammation, edema, and degeneration following administration of desmopressin (8). The expression of the V2 receptor was increased following desmopressin administration. It also led to a reduction in IL-1ß, TNF-α, and NF-κB levels. The protective effect of desmopressin on flap survival was reversed upon giving SR-49059. The optical imaging revealed enhanced blood flow in the desmopressin group compared to the control group. CONCLUSIONS: Desmopressin could be repurposed to improve flap survival. V1a and V2 receptors probably mediate this effect.

Arginine vasopressin hormone receptor antagonists in experimental autoimmune encephalomyelitis rodent models: A new approach for human multiple sclerosis treatment.

Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease that affects the central nervous system. MS is a heterogeneous disorder of multiple factors that are mainly associated with the immune system including the breakdown of the blood-brain and spinal cord barriers induced by T cells, B cells, antigen presenting cells, and immune components such as chemokines and pro-inflammatory cytokines. The incidence of MS has been increasing worldwide recently, and most therapies related to its treatment are associated with the development of several secondary effects, such as headaches, hepatotoxicity, leukopenia, and some types of cancer; therefore, the search for an effective treatment is ongoing. The use of animal models of MS continues to be an important option for extrapolating new treatments. Experimental autoimmune encephalomyelitis (EAE) replicates the several pathophysiological features of MS development and clinical signs, to obtain a potential treatment for MS in humans and improve the disease prognosis. Currently, the exploration of neuro-immune-endocrine interactions represents a highlight of interest in the treatment of immune disorders. The arginine vasopressin hormone (AVP) is involved in the increase in blood-brain barrier permeability, inducing the development and aggressiveness of the disease in the EAE model, whereas its deficiency improves the clinical signs of the disease. Therefore, this present review discussed on the use of conivaptan a blocker of AVP receptors type 1a and type 2 (V1a and V2 AVP) in the modulation of immune response without completely depleting its activity, minimizing the adverse effects associated with the conventional therapies becoming a potential therapeutic target in the treatment of patients with multiple sclerosis.

Blockade of vasopressin receptors reduces the threshold pressure of micturition reflex in female rats.

The mechanisms involved in urinary bladder control are not fully understood, but it is well accepted that a complex central network is involved in micturition control. The micturition reflex can be modulated by direct cortical influence through facilitatory and inhibitory mechanisms. In addition, humoral mechanisms are involved in the bladder control. Vasopressin increases bladder contraction and intravesical pressure. This study sought to investigate the effect of intravenous injections of vasopressin receptor antagonists on cystometric parameters in anesthetized female rats. Isoflurane anesthetized adult female Wistar rats underwent femoral artery and vein cannulation for arterial pressure (AP) and heart rate (HR) recordings, and infusion of drugs, respectively. The bladder was also cannulated for intravesical pressure (IP) recordings and infusion of saline (10 mL/h) for cystometric evaluation. After baseline AP, HR and IP recordings, saline (vehicle, 1 mL/kg), V1a (5 µg/kg) or V2 receptor antagonist (5 µg/kg) was injected i.v. and after 25 min the cystometry was carried out. Neither saline nor V1a or V2 receptor blockade evoked any change in AP, HR and IP. Nevertheless, during cystometry, the threshold pressure of the micturition reflex was significantly reduced in rats with V1a (to 19.30 ± 2.39 mmHg) and V2 receptor blockade (to 19.88 ± 2.49 mmHg) compared to the saline group (28.85 ± 2.06 mmHg, p = 0.014). No difference was observed in the other cystometric parameters. Therefore, the data suggest that blockade of V1a and V2 receptors reduces the threshold pressure of the micturition reflex and does not influence other cystometric parameters in anesthetized female Wistar rats.

Oxytocin and vasopressin in the hippocampus.

Oxytocin (OXT) and vasopressin (AVP) are related neuropeptides that exert a wide range of effects on general health, homeostasis, development, reproduction, adaptability, cognition, social and nonsocial behaviors. The two peptides are mainly of hypothalamic origin and execute their peripheral and central physiological roles via OXT and AVP receptors, which are members of the G protein-coupled receptor family. These receptors, largely distributed in the body, are abundantly expressed in the hippocampus, a brain region particularly vulnerable to stress exposure and various lesions. OXT and AVP have important roles in the hippocampus, by modulating important processes like neuronal excitability, network oscillatory activity, synaptic plasticity, and social recognition memory. This chapter includes an overview regarding OXT and AVP structure, synthesis, receptor distribution, and functions, focusing on their relationship with the hippocampus and mechanisms by which they influence hippocampal activity. Brief information regarding hippocampal structure and susceptibility to lesions is also provided. The roles of OXT and AVP in neurodevelopment and adult central nervous system function and disorders are highlighted, discussing their potential use as targeted therapeutic tools in neuropsychiatric diseases.

Use of BRET to Measure ß-Arrestin Recruitment at Oxytocin and Vasopressin Receptors.

Bioluminescence resonance energy transfer (BRET) is a cutting-edge biophysical technique used for exploring G protein-coupled receptor (GPCR) pharmacology. BRET relies on the nonradiative energy transfer from a luciferase energy donor to an acceptor fluorophore after oxidation of a luciferase substrate. This energy transfer occurs only if the donor and acceptor are within close proximity. Over the past few years, BRET has been successfully applied to study GPCR oligomerization as well as interactions of receptors with G proteins, G protein-coupled receptor kinases (GRKs), or ß-arrestins. Herein, we describe how BRET can be applied to study signaling at the oxytocin receptor (OTR) and vasopressin receptors, thereby enabling the identification of (biased) ligands and molecular probes for investigating receptor functionality.

[Perpendicular and transverse needling of "Sanyinjiao" (SP6) relieves abdominal pain by regulating arginine vasopressin and its receptor expression levels in uterus and hypothalamus in cold-stasis type dysmenorrhea rats].

OBJECTIVE: To observe the effect of perpendicular and subcutaneous transverse needling at "Sanyinjiao" (SP6) on visceral pain behavior, arginine vasopressin (AVP) content in the serum, uterine tissues, spinal cord and hypothalamus and expression of AVP receptors AVPR1A and AVPR1B in the uterine tissues, spinal cord and hypothalamus in cold-stasis (stasis due to pathogenic cold) type dysmenorrhea rats, so as to explore their mechanisms underlying pain relief. METHODS: Forty female SD rats were randomly divided into blank control, model, perpendicular needling and transverse needling groups, with 10 rats in each group. The cold-stasis dysmenorrhea rat model was established by exposure in a freezer (-25 ℃) for 4 h, once daily for 5 days, and subcutaneous injection of estradiol benzoate (once daily for 10 days) and intra-abdominal injection of oxytocin injection (once). For rats of the two acupuncture groups, acupuncture needles were inserted into the bilateral SP6 perpendicularly or transversely to a depth of about 4-5 mm, and retained for 20 min. The abdominal pain behavior was assessed by recording the writhing latency and scaling the rats' writhing reactions after modeling. The contents of AVP in the serum, uterus, spinal cord and hypothalamus tissues were assayed using ELISA and the expression of AVPR1A and AVPR1B in the uterus, spinal cord and hypothalamus was measured by using Western blot and quantitative real time-PCR, respectively. RESULTS: After mode-ling and compared with the blank control group, the writhing latency was significantly shortened (P<0.05), and the writhing score in the first 20 min was significantly increased (P<0.01) in the model group. After the intervention, the writhing latency was significantly prolonged (P<0.01), and the writhing scores in 20 min were significantly decreased (P<0.01) in the two needling groups. The AVP contents were obviously increased in the serum and uterine tissue (P<0.05, P<0.01) but decreased appa-rently in the spinal cord and hypothalamus tissues (P<0.01, P<0.05), and the expression levels of AVPR1A or AVPR1B protein and mRNA were markedly increased in the uterine tissues (P<0.01, P<0.05), and significantly decreased in the spinal cord and hypotha-lamus in the model group relevant to the control group (P<0.05, P<0.01). Following the intervention, The AVP content in the serum of the perpendicular needling group (P<0.05) and that in the uterus of the two needling groups were significantly decreased (P<0.01), as well as that in the hypothalamus was obviously increased in the two needling groups (P<0.05). The expression levels of AVPR1A protein and mRNA in the uterus were significantly down-regulated in the two needling groups (P<0.01, P<0.05) and AVPR1B protein in the hypothalamus of the perpendicular needling group was up-regulated (P<0.05). Moreover, no significant differences were found between the two needling groups in regulating the related indexes mentioned above (P>0.05). CONCLUSION: Both perpendicular and subcutaneous transverse needling at SP6 have an immediate analgesic effect in cold-stasis type dysmenorrhea rats, which may be related to their effects in regulating AVP levels and its receptor expression in the uterine and hypothalamus.

Vasopressin and v1br gene expression is increased in the hypothalamic pvn of borderline hypertensive rats.

Vasopressin (VP) is a neurohypophyseal peptide best known for its role in maintaining osmotic and cardiovascular homeostasis. The main sources of VP are the supraoptic and paraventricular (PVN) nuclei of the hypothalamus, which coexpress the vasopressin V1a and V1b receptors (V1aR and V1bR). Here, we investigated the level of expression of VP and VP receptors in the PVN of borderline hypertensive rats (BHRs), a key integrative nucleus for neuroendocrine cardiovascular control. Experiments were performed in male BHRs and Wistar rats (WRs) equipped with a radiotelemetry device for continuous hemodynamic recording under baseline conditions and after saline load without or with stress. Autonomic control of the circulation was evaluated by spectral analysis of blood pressure (BP) and heart rate (HR) variability and baroreceptor reflex sensitivity (BRS) using the sequence method. Plasma VP was determined by radioimmunoassay, and VP, V1aR, and V1bR gene expression was determined by RT-qPCR. Under baseline conditions, BHRs had higher BP, lower HR, and stronger BRS than WRs. BP and HR variability was unchanged. In the PVN, overexpression of the VP and V1bR genes was found, and plasma VP was increased. Saline load downregulated V1bR mRNA expression without affecting VP mRNA expression or plasma VP and BP. Adding stress increased BP, HR, and low-frequency sympathetic spectral markers and decreased plasma VP without altering the level of expression of VP and VP receptors in the PVN. It follows that overexpression of VP and V1bR in the PVN is a characteristic trait of BHRs and that sympathetic hyperactivity underlies stress-induced hypertension.

Vasopressin and vasopressin receptors in brain edema.

Vasopressin is a peptide hormone produced in the hypothalamus and released from the posterior pituitary. Secretion of vasopressin is followed by activation of its receptors V1a, V1b, and V2 throughout the body. Each receptor type is responsible for a specific function of vasopressin. For example, V1a receptor activation triggers vasoconstriction, V1b receptor is responsible for modulation of mood and behavior, and V2 receptor induces water reabsorption in the kidney. Vasopressin is known to regulate blood pressure, blood osmolality, and blood volume. The effects of V1a and V2 receptors can be amplified when vasopressin is secreted in excessive amounts, and this condition may be experienced by patients undergoing a disease or stress. In pathological conditions such as stroke, traumatic brain injury, subarachnoid hemorrhage, liver disease, and other diseases, vasopressin can exacerbate brain edema. Oversecretion of vasopressin unleashes deleterious pathways leading to hyponatremia and brain edema. This book chapter describes important mechanisms and pathways linking vasopressin and brain edema triggered by various conditions.

The influence of post-infarct heart failure and high fat diet on the expression of apelin APJ and vasopressin V1a and V1b receptors.

Vasopressin and apelin are reciprocally regulated hormones which are implicated in the pathophysiology of heart failure and the regulation of metabolism; however, little is known about their interactions under pathological conditions. In this study, we determined how post-infarct heart failure (HF) and a high fat diet (HFD) affect expression of the apelin APJ receptor (APJR) and the V1a (V1aR) and V1b (V1bR) vasopressin receptors in the hypothalamus, the heart, and the retroperitoneal adipose tissue. We performed experiments in male 4-week-old Sprague Dawley rats. The animals received either a normal fat diet (NFD) or a HFD for 8 weeks, then they underwent left coronary artery ligation to induce HF or sham surgery (SO), followed by 4 weeks of NFD or HFD. The HF rats showed higher plasma concentration of NT-proBNP and copeptin. The HF reduced the APJR mRNA expression in the hypothalamus. The APJR and V1aR protein levels in the hypothalamus were regulated both by HF and HFD, while the V1bR protein level in the hypothalamus was mainly influenced by HF. APJR mRNA expression in the heart was significantly higher in rats on HFD, and HFD affected the reduction of the APJR protein level in the right ventricle. The regulation of APJR, V1aR and V1bR expression in the heart and the retroperitoneal adipose tissue were affected by both HF and HFD. Our study demonstrates that HF and HFD cause significant changes in the expression of APJR, V1aR and V1bR, which may have an important influence on the cardiovascular system and metabolism.

Vasopressin in Heart Failure.

BACKGROUND AND OBJECTIVE: The nonapeptide hypothalamic hormone vasopressin (VP), exerts important effects on cardiovascular system via its receptors V1, V2 and V3. Patients with congestive heart failure (CHF) present elevated plasma VP levels. Aim of this paper is to review the role of vasopressin in CHF. METHODS: We analyzed the best of published literature dealing with the role of VP in patients affected by CHF, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on August 2017. RESULTS: Scientific articles dealing with the relationship between VP and CHF show that circulating high VP levels found in CHF despite an exaggerated increase in circulatory blood volume can contribute to CHF exacerbation. In particular, the stimulation of V1R induces vascular constriction responsible for increased systemic vascular resistance and afterload, and, in addition, coronary vasoconstriction with consequent reduced coronary circulation and cardiac contractility, whereas the stimulation of V2R induces free water reabsorption and this is responsible of preload increase and congestion of pulmonary vascular bed with edema and hyponatremia, markers of advanced CHF. CONCLUSION: VP can play an important role among the derangements of the endocrine system in CHF even being a possible target in the treatment of this condition. Vaptans, antagonists of VP receptors, in fact, are able to increase urine output and plasma sodium levels without the increased risk of arrhythmic death induced by diuretics, even though, further studies are needed to establish a possible role of these drugs in the treatment of CHF.