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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested whether severe congestive heart failure (CHF), a condition associated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting duct. CHF was induced by left coronary artery ligation. Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pressures (LVEDP): 26.9 +/- 3.4 vs. 4.1 +/- 0.3 mmHg, and reduced plasma sodium concentrations (142.2 +/- 1. 6 vs. 149.1 +/- 1.1 mEq/liter). Quantitative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 +/- 53%, n = 12) relative to sham-operated controls (100 +/- 13%, n = 14). In contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective. Furthermore, postinfarction animals without LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 +/- 28% of sham levels, n = 6). Immunocytochemistry and immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellular vesicles in collecting duct cells from rats with severe CHF, consistent with enhanced trafficking of AQP2 to the apical plasma membrane. The selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retention and hyponatremia in severe CHF.
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PMID:Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct. 914 58

The recent discovery of aquaporins, a family of highly conserved water channel proteins, which are expressed in both eukaryotes and prokaryotes, has provoked a re-evaluation of the physiology of water transport in all organisms. So far, seven distinct aquaporins have been characterised in mammals, but highly homologous family members have also been found in amphibians, insects, plants and bacteria. These transmembrane proteins serve to facilitate water transport down osmotic gradients with low activation energy. Alterations in channel expression, cellular targeting and perhaps channel permeability regulate membrane water transport. Naturally occurring and experimentally produced mutations in aquaporins cause a variety of perturbations of water homeostasis. Manipulation of aquaporin expression may have a therapeutic role in several disease processes including cardiac failure and the ascites associated with liver disease.
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PMID:The aquaporins. A family of water channel proteins. 960 69

Central to a unifying hypothesis of body fluid regulation is maintenance of arterial circulatory integrity. This may be disturbed by arterial underfilling, either from reduction in cardiac output or by peripheral arterial vasodilation. In cardiac failure (CF), cardiac output falls and the nonosmotic release of arginine vasopressin (AVP) and expression of AVP mRNA in the hypothalamus are stimulated. V2 AVP receptor antagonists correct the impaired water excretion in rats with low-output CF, increase solute free water clearance, correct the hyponatremia in congestive CF patients, and normalize urinary concentrations of the aquaporin-2 (AQP-2) water channels. In conditions associated with peripheral vasodilation, such as cirrhosis, nonosmotic release of AVP also occurs, and AQP-2 gene expression in the rat kidney is up-regulated. In cirrhosis, nitric oxide-mediated vasodilation occurs early prior to water retention. V2 antagonists reverse the latter. In normal pregnancy, plasma AVP is relatively high for the degree of hypoosmolality. Pregnant rats up-regulate AQP-2 in the renal papilla, an effect reversed by V2 receptor antagonists. This supports the hypothesis that AVP is an important mediator of renal water retention in pregnancy. In summary, AVP-mediated water retention through collecting duct AQP-2 water channels is important in both low-output CF and high-output states such as cirrhosis and pregnancy. V2 receptor antagonists reverse the water retention and down-regulate AQP-2 water channels.
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PMID:Pathophysiology of renal fluid retention. 973 67

Vasopressin (AVP) is released in response to both osmotic and nonosmotic stimuli. Nonosmotic-stimulated AVP release occurs in cardiac failure, cirrhosis, and pregnancy in response to alterations in arterial circulatory integrity. Cardiac failure in rats is associated with increased plasma AVP and hypothalamic AVP mRNA, and in humans, it is associated with cardiac failure. Plasma AVP concentrations are elevated when measured with a sensitive radioimmunoassay. Urinary concentrations of AVP-responsive aquaporin-2 water channels are also elevated in cardiac failure. V2 receptor antagonists correct the impaired solute-free water excretion seen in rats with low-output cardiac failure and reverse the upregulation of renal aquaporin-2 water channels. Orally active non-peptide-selective V2 receptor antagonists administered to patients with congestive cardiac failure decrease urinary concentrations of aquaporin-2, increase solute-free water clearance, and correct the hyponatremia. Cirrhosis of the liver results in splanchnic arterial vasodilation and increased vascular capacity, most likely secondary to increased nitric oxide production. This relative underfilling of the arterial circulation stimulates nonosmotic AVP release with resultant water retention. Aquaporin-2 gene expression is upregulated in the kidneys of rats with cirrhosis of the liver. AVP-2 receptor antagonists administered to animals with cirrhosis reverse the water retention. Human studies using orally active, non-peptide-selective V2 receptor antagonists in patients with cirrhosis are currently underway. Pregnancy is another state of nitric oxide-mediated arterial vasodilation that is associated with plasma AVP concentrations that are relatively high for the degree of hypoosmolality. Upregulation of the water channel aquaporin-2 in the renal papillae of pregnant rats has also been demonstrated, and this effect is reversed by administration of a V2 receptor antagonist.
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PMID:Vasopressin release, water channels, and vasopressin antagonism in cardiac failure, cirrhosis, and pregnancy. 975 91

The recent identification of aquaporin water channel proteins has provided detailed information about the molecular basis for transepithelial water transport. At least five aquaporins have been identified in the kidney; they have provided detailed molecular insight into the fundamental physiology of water balance. This article focuses primarily on the physiology and pathophysiologic significance of the vasopressin-regulated water channel aquaporin-2 (AQP2) in a number of conditions where body water balance is disturbed. AQP2 is regulated by vasopressin by both short- and long-term mechanisms. Acutely, vasopressin induces exocytic insertion of AQP2 into the apical plasma membrane to increase collecting duct water reabsorption. Moreover, long-term regulation of body water balance is achieved by changes in total collecting duct levels of AQP2. Recent studies have documented that both vasopressin and vasopressin-independent regulation play important roles in this. In conditions with acquired nephrogenic diabetes insipidus (eg, lithium treatment, hypokalemia, postobstructive polyuria), AQP2 expression and targeting have been found to be markedly reduced, providing an explanation for the polyuria and the inability to concentrate urine associated with these conditions. Conversely, in conditions with water retention (eg, heart failure, pregnancy), it has been shown that AQP2 levels and plasma membrane targeting are increased. Continued analysis of aquaporins is providing detailed molecular insight into the physiology and pathophysiology of water balance disorders.
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PMID:Pathophysiology of aquaporin-2 in water balance disorders. 982 11

The pathophysiology of sodium and water retention in heart failure is discussed in the context of a unifying hypothesis of body fluid volume regulation. Critical to this hypothesis is the maintenance of arterial circulatory integrity, which can be disturbed by either a reduction in cardiac output or a fall in systemic vascular resistance secondary to arterial vasodilatation, as seen in high output heart failure. The filling of the arterial circulation is sensed by receptors in the left ventricle, carotid artery, aortic arch and renal afferent arteriole. Effector mechanisms involve non-osmotic vasopressin synthesis and release, the renin-angiotensin-aldosterone system and the sympathetic nervous system. In low output heart failure non-peptide selective orally active vasopressin V2-receptor antagonists correct the hyponatremia, hypoosmolality, and water retention and decrease urinary aquaporin-2 water channels, supporting the role of vasopressin in the water retention seen in heart failure. In advanced heart failure aldosterone escape does not occur because of diminished distal delivery of sodium which also contributes to the resistance to atrial natriuretic peptide seen in heart failure. In high output cardiac failure arterial underfilling associated with arterial vasodilation stimulates activation of neurohumoral systems. Tailored specific selective inhibition of these neurohumoral systems, perhaps in combination, may enable more effective treatment of cardiac failure.
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PMID:Pathogenesis of sodium and water retention in cardiac failure. 983 76

Hyponatremia is common in advanced heart failure and relates to the severity of the disease. Non-osmotic arginine vasopressin (AVP) release and biosynthesis have been shown to be increased during chronic cardiac failure (CHF) and baroreceptors pathways have been demonstrated to play a major role in this non-osmotic stimulation of AVP. Decreased cardiac output unloads the baroreceptors and activates the sympathetic nervous system, thus stimulating AVP through a separate pathway which overrides the osmotic pathway. Besides sympathetic nervous system activation, neurohumoral peptides, such as angiotensin II, endothelins, natriuretic peptides and prostaglandins, could also participate in the non-osmotic AVP activation. The vasoconstrictor effect of AVP has been supported by the decrease systemic vascular resistance during the administration of V1 receptor AVP antagonist in CHF patients. Administration of V2 receptor AVP antagonists corrects the hyponatremia and has been demonstrated to improve survival in animal models of heart failure. Preliminary data in humans with CHF also demonstrate urinary dilution and correction of hyponatremia with orally active non-peptide V2 receptor antagonists. Finally, upregulation of the AVP-regulated water channels, aquaporin-2 (AQP2), located in the collecting duct cells has been shown in experimental heart failure. This AQP2 upregulation can be entirely suppressed by V2 receptor AVP antagonists paralleling the correction of the hyponatremia. Thus, non-osmotic release of AVP in CHF upregulates AQP2 water channels, enhances water reabsorption and causes hyponatremia. The V1, and perhaps the V2, receptor activation may also diminish cardiac function.
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PMID:Recent advances in the understanding of water metabolism in heart failure. 1002 33

Heart failure is a leading cause of morbidity and mortality. In the United States, there are more than 5 million patients with heart failure and over 500,000 newly diagnosed cases each year. Numerous advances have been made in our understanding of the pathophysiologic mechanisms contributing to sodium and water retention in this condition. Important alterations in the sympathetic nervous system and the renin-angiotensin-aldosterone system have been described in heart failure, allowing the use of mechanism-specific treatments such as beta-adrenergic receptor antagonism and angiotensin-converting enzyme inhibition. As our understanding of the roles of the natriuretic peptides and the arginine vasopressin-aquaporin-2 system in the pathophysiology of heart failure evolves, treatments directed toward the alterations in these systems in heart failure can be further developed.
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PMID:Pathophysiology of sodium and water retention in heart failure. 1180 79

Alterations in water metabolism are present in conditions such as diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, cardiac failure, cirrhosis, and pregnancy. Recent advances in molecular biology have enhanced our understanding of disordered water metabolism in these conditions. This review examines the roles of central vasopressin synthesis and release and collecting duct vasopressin V2 receptor and aquaporin-2 water channel regulation in water-losing and water-retaining states.
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PMID:Water-losing and water-retaining states: role of water channels and vasopressin receptor antagonists. 1197 94

The aquaporins are a family of small, integral membrane proteins that function as plasma membrane transporters of water and in some cases small polar solutes such as glycerol. There are at least 10 distinct aquaporins in mammals with specific patterns of expression in epithelial, endothelial and other tissues. Recent studies in aquaporin-null mice have indicated key roles for certain aquaporins in the urinary concentrating mechanism, fluid secretion by glands, brain swelling, skin moisture, hearing and vision, and gastrointestinal absorption. The only known inhibitors of some aquaporins are mercurial sulfhydryl-reactive compounds, which are too toxic and nonspecific for use in vivo. Small-molecule or peptide aquaporin blockers have potential applications in the treatment of disorders of fluid/pressure homeostasis such as heart failure, hypertension, brain swelling and glaucoma.
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PMID:Applications of aquaporin inhibitors. 1281 84


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