Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mortality and morbidity of patients with heart failure (HF) remains unacceptably high despite current advances in medical therapies. In recent years, rapid growth in understanding the pathophysiology of heart failure has allowed for insights into many potential new therapeutic strategies. Yet until now, despite sound biological basis for efficacy and success in early-phase studies, novel agents have not stood up to the scrutiny of late-phase clinical trials. This review will examine the key emerging therapies for acute decompensated heart failure (ADHF), in light of available pathophysiological and clinical evidence. Several new agents for ADHF use novel mechanisms of action that focus on new treatment targets, such as those providing anti-ischemic and anti-stunning effects, blocking vasopressin receptors, blocking endothelin-1 receptors, or endogenous cardiac neurohormones and B-type natriuretic peptide (BNP).
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PMID:Emerging drug therapies for the management of acute decompensated heart failure. 1807 92

Simple, sensitive and specific predictors of mortality in the critically ill remain elusive goals, and brain natriuretic peptide and venous lactate are the subjects of recent studies. The role of vasopressin in sepsis continues to be the focus of much research interest. Dose ranging studies, potential adverse effects, and selective V1 agonists are discussed below in recent trials. Finally the use of erythropoietin in the critically ill continues to be studied but many continue to urge caution for widespread use outside of clinical trials.
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PMID:Recently published papers: predictors, pressors and poietins. 1819 Jul 27

One of the most important comorbidities in heart failure is renal dysfunction. Diminished estimated glomerular filtration rate is a potent predictor of cardiovascular mortality and complications. On the other hand, worsening heart failure or acute decompensated heart failure can accelerate worsening of renal function--the so-called cardiorenal syndrome. Risk factors include hypertension, diabetes, elderly age, and prior history of heart or renal failure. The pathophysiology of the cardiorenal syndrome involves intrarenal hemodynamics, transrenal perfusion pressure and systemic neurohormonal factors. Clinical management of the patient with cardiorenal syndrome includes the challenge of diuretic resistance, which may involve correcting the underlying cause, combination diuretics or diuretic infusions. The key to improved outcome is the optimization of proven heart failure therapies. The use of vasodilator therapy is the current mainstay of treatment. Nesiritide, or recombinant B-type natriuretic peptide, has courted controversy regarding its role in cardiorenal syndrome. However, data are emerging that low doses appear to be renal-protective. Other more recent strategies include ultrafiltration, vasopressin antagonists and adenosine antagonists. All of these newer modalities promise more rapid volume removal, but their ultimate impact on survival or preservation of renal function is unknown at the present time. Because of the complex nature of these patients, and the compromised outcome, it is important that cardiologists, nephrologists and internists all work together toward the common goal of protecting the patient with cardiorenal syndrome, and use the best available evidence for management.
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PMID:Cardiorenal syndrome in heart failure: a cardiologist's perspective. 1862 86

The present study sought to identify confounding factors for the interpretation of copeptin levels in healthy individuals. The natriuretic peptides are recognized as diagnostic and prognostic tools in HF (heart failure). Interpretation of BNP (brain natriuretic peptide) and NTproBNP (N-terminal pro-BNP) levels is multifaceted as their secretion is influenced by many variables. A newly identified glycopeptide called copeptin is comparable with the natriuretic peptides in the diagnosis and prognosis of HF and as a prognostic biomarker after AMI (acute myocardial infarction). Copeptin, derived from the C-terminal portion of the precursor to AVP (arginine vasopressin), is secreted stoichiometrically with vasopressin, hence it can be used as a surrogate marker of the AVP system. In the present study, 706 healthy volunteers were recruited from a local HF screening study. Participants with a history of cardiovascular disease and those with echocardiographic abnormalities were excluded from the study. Copeptin and NTproBNP levels were assayed using in-house immunoluminometric assays. Median copeptin levels were significantly higher in the male volunteers compared with the females [median (range): 4.3 (0.4-44.3) compared with 3.2 (1.0-14.8) pmol/l; P<0.001]. In males, copeptin was correlated with eGFR (estimated glomerular filtration rate; r(s)=-0.186, P<0.001). In females, the correlation of copeptin with eGFR was weak (r(s)=-0.097, P=0.095). DT (deceleration time) and left atrial size correlated with higher copeptin levels (r(s)=0.085, P=0.029 and r(s)=0.206, P<0.001 respectively). Only gender (P<0.001), eGFR (P<0.001), left atrial size (P=0.04) and DT (P=0.02) remained independently predictive of plasma copeptin. The present study suggests that gender and renal function specific partition values should be used to interpret copeptin values in future studies of this biomarker in HF or ischaemic heart disease.
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PMID:Gender and renal function influence plasma levels of copeptin in healthy individuals. 1864 34

Hypotonic fluids are commonly used for treating hospitalized children. However, an excess of arginine vasopressin (AVP) with impaired free water excretion is thought to contribute to the development of hyponatremia in febrile children. The aim of this two-part study was to define the clinical relationship between hyponatremia and excess AVP. In a retrospective study carried out between 2001 and 2005, we found that approximately 17% of the hospitalized patients had hyponatremia [serum sodium (Na) < 135 mEq/l] upon admission and that the ratio of patients with hyponatremia was significantly higher among febrile patients than among afebrile patients. In a subsequent prospective study, we examined 73 hospitalized patients who presented with acute febrile diseases accompanied by hyponatremia (serum Na <134 mEq/l). Almost all of these patients demonstrated excess AVP, defined as high plasma AVP levels (>1 pg/ml). There were no significant relationships between the levels of AVP and other laboratory variables, including serum sodium, serum osmolality, atrial natriuretic peptide, and brain natriuretic peptide. About 30% (22/73) of the patients fulfilled the criteria of the syndrome of inappropriate secretion of antidiuretic hormone. These findings suggest that fever and other nonosmotic stimuli lead directly to excess AVP and hyponatremia. We therefore recommend that isotonic fluids should be used for patients with prolonged fever and hyponatremia.
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PMID:Hyponatremia due to an excess of arginine vasopressin is common in children with febrile disease. 1904

Polycystic kidney diseases result from disruption of the genetically defined program that controls the size and geometry of renal tubules. Cysts which frequently arise from the collecting duct (CD) result from cell proliferation and fluid secretion. From mCCD(cl1) cells, a differentiated mouse CD cell line, we isolated a clonal subpopulation (mCCD-N21) that retains morphogenetic capacity. When grown in three-dimensional gels, mCCD-N21 cells formed highly organized tubular structures consisting of a palisade of polarized epithelial cells surrounding a cylindrical lumen. Subsequent addition of cAMP-elevating agents (forskolin or cholera toxin) or of membrane-permeable cAMP analogs (CPT-cAMP) resulted in rapid and progressive dilatation of existing tubules, leading to the formation of cystlike structures. When grown on filters, mCCD-N21 cells exhibited a high transepithelial resistance as well as aldosterone- and/or vasopressin-induced amiloride-sensitive and -insensitive current. The latter was in part inhibited by Na(+)-K(+)-2Cl(-) cotransporter (bumetanide) and chloride channel (NPPB) inhibitors. Real-time PCR analysis confirmed the expression of NKCC1, the ubiquitous Na(+)-K(+)-2Cl(-) cotransporter and cystic fibrosis transmembrane regulator (CFTR) in mCCD-N21 cells. Tubule enlargement and cyst formation were prevented by inhibitors of Na(+)-K(+)-2Cl(-) cotransporters (bumetanide or ethacrynic acid) or CFTR (NPPB or CFTR inhibitor-172). These results further support the notion that cAMP signaling plays a key role in renal cyst formation, at least in part by promoting chloride-driven fluid secretion. This new in vitro model of tubule-to-cyst conversion affords a unique opportunity for investigating the molecular mechanisms that govern the architecture of epithelial tubes, as well as for dissecting the pathophysiological processes underlying cystic kidney diseases.
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PMID:cAMP-dependent chloride secretion mediates tubule enlargement and cyst formation by cultured mammalian collecting duct cells. 1905 3

AMP-activated protein kinase (AMPK) is a regulatory kinase coupling cellular metabolism with ion transport. Madin-Darby Canine Kidney-Clone 7 (MDCK-C7) cells possess characteristics of the renal principal cell type, express the cystic fibrosis transmembrane regulator and the epithelial Na(+) channel, and display NPPB and amiloride-sensitive transepithelial transport when stimulated with [Arg(8)]-vasopressin. [Arg(8)]-vasopressin binding to its receptor on the basolateral membrane of MDCK-C7 results in cAMP production, activation of cAMP-dependent protein kinase A (PKA), and increases in Cl(-) and Na(+) transport. Ussing-style electrophysiology showed that the PKA inhibitor, H89, blocked Cl(-) and Na(+) transport. Unexpectedly, [Arg(8)]-vasopressin stimulation resulted in the dephosphorylation of pAMPK(thr172). H89 did not prevent this, suggesting that the dephosphorylation is independent of PKA. 24 hour, but not 15 minute, incubation with the AMPK activator, AICAR, also blocked [Arg(8)]-vasopressin-stimulated currents. Contrary to previous studies, immunoblotting revealed that AICAR did not increase abundance of the active, phosphorylated form of AMPK (pAMPK(thr172)); although, AICAR treatment significantly blocked [Arg(8)]-vasopressin -stimulated cAMP production. [Arg(8)]-vasopressin still caused pAMPK(thr172) dephosphorylation in the presence of AICAR, suggesting that this effect is also independent of cAMP. In summary, these data suggest [Arg(8)]-vasopressin regulates AMPK phosphorylation and that AICAR inhibits ion transport independently of AMPK in MDCK-C7 cells.
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PMID:Vasopressin regulates the phosphorylation state of AMP-activated protein kinase (AMPK) in MDCK-C7 cells. 1908 30

Abstract It is not entirely clear whether or not atrial natriuretic peptide (ANP) directly inhibits vasopressin neurons in the supraoptic nucleus (SON) and paraventricular nucleus. Recently, a novel peptide, brain natriuretic peptide (BMP), which has been isolated from the brain, has been shown to have a similar action to ANP on the regulation of vasopressin release. Intracerebroventricular injection of both BNP and ANP inhibits stimulus-evoked increases of plasma vasopressin level. The present study was undertaken: 1) to investigate whether BNP affects the activity of neurons in the region of the anteroventral third ventricle (AV3V) and SON which are involved in the control of body fluid homeostasis and blood pressure regulation, 2) to reassess effects of ANP on SON neurons, and 3) to test whether BNP exerts its effects by mechanisms which are different from those of ANP. Extracellular recordings were made from 213 AV3V and 110 SON spontaneously firing neurons in the rat coronal hypothalamic slice preparation. Of the AV3V neurons tested, BNP inhibited 86 (40%) and excited 2 (1%) while 125 neurons remained unaffected. A dose-response relationship was obtained for 7 AV3V neurons at different BNP concentrations ranging from 10(-11) M to 10(-6) M; the firing rates of all 7 neurons decreased. The threshold concentration to evoke inhibitory responses was approximately 10(-10)M in the AV3V. When BNP and ANP were applied to the same neuron, most AV3V neurons which were inhibited by BNP were also inhibited by ANP and the neurons which were unaffected by BNP were also unaffected by ANP. Thus, these two peptides probably have a similar action on AV3V neurons. When BNP and angiotensin II were applied to a group of 60 neurons in the AV3V, most of the responsive neurons showed either inhibitory responses to BNP or excitatory responses to angiotensin II. Both BNP and ANP were applied to a group of 110 SON neurons: BNP (10 (-7) M) inhibited 52 (75%) of 69 phasic (putative vasopressin) neurons, while BNP affected none of the 41 non-phasic (putative oxytocin) neurons. By contrast, ANP inhibited only 20 (29%) of 69 phasic neurons tested but it also had no effect on 41 non-phasic neurons tested. Our results are consistent with the suggestion that BNP is involved in the regulation of vasopressin release by acting on SON neurons and AV3V neurons.
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PMID:Inhibition by brain natriuretic Peptide of vasopressin neurons in the supraoptic nucleus and neurons in the region of the anteroventral third ventricle in rat hypothalamic slice preparations. 1921 45

Heart failure results in significant morbidity and mortality in the United States. Chronic heart failure is often complicated by renal insufficiency. Further, acute decompensated heart failure is often complicated by worsening renal function or the development of diuretic resistance. Heart failure complicated by renal dysfunction has a significantly worse prognosis. The pathophysiology underlying this so-called cardiorenal syndrome (CRS) is unclear. It likely involves a combination of maladaptive neurohormonal activation and renal homeostatic mechanisms. The treatment (including recombinant B-type natriuretic peptide, ultrafiltration, continuous furosemide infusions and vasopressin antagonists) has thus far been marginally successful at best. Further research into the mechanism and treatment of CRS is required.
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PMID:Organ cross talk in the critically ill: the heart and kidney. 1927 Apr 50

The aims of the present study were to determine whether natriuretic peptide receptors coupled to guanylate cyclase are present in the neural lobe (NL) of the pituitary and eventually localized on pituicytes and/or on nerve fibers and whether cyclic GMP may be involved in the regulation of vasopressin secretion. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) enhanced cyclic GMP content of NLs in a dose-related fashion, with ED(50) values of about 5 x 10(-8)M, while CNP failed to significantly elevate guanylate cyclase activity. ANP stimulated cyclic GMP accumulation in NLs lacking functional nerve fibers, while it was without significant effect on isolated nerve terminals. In the brain, ANP-enhanced cyclic GMP production was similarly expressed in glial and not in neuronal cultures, although intracellular guanylate cyclase activity (stimulated by sodium nitroprusside) was present in both cell types. Finally, the cell permeant S-bromoguanosine 3':5'-monophosphate GMP failed to change either basal or isoproterenol-stimulated vasopressin secretion from incubated NLs. We conclude that in the NL, as well as in brain tissue cultures, the guanylate cyclase-NP receptor complex (most probably the ANP-A subtype) is localized on pituicytes/filial cells rather than on nerve fibers/cells and that cyclic GMP may not be directly involved in the regulation of vasopressin output from the NL.
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PMID:Evidence for the presence of guanylate cyclase-coupled receptors for atrial natriuretic peptide on pituicytes of the neurohypophysis. 1991 20


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