Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasopressin, like all the other neuro-hormonal systems, is activated in patients with cardiac insufficiency. Vasopressin attaches itself to two distinct specific receptors. It is through the intermediary of the renal V2 receptor, controlling the reabsorption of water by the collecting duct, that vasopressin finely regulates the blood osmolarity. The ubiquitous V1a receptor is essentially responsible for the vasoconstrictor effect of the hormone. Some specific antagonists for these two receptors have now been evaluated in various pathologies such as SIADH, cirrhosis or cardiac insufficiency. In this situation the mixed antagonists, anti-V1a-V2, seem more appropriate than the specific V1a or V2 receptor antagonists. The results of the first human studies are encouraging. The mixed antagonists reduce the pulmonary capillary pressure and increase diuresis and clearance of free water. But further studies are necessary to confirm these results and to demonstrate a reduction in morbidity and mortality before adding this class of medication to the therapeutic arsenal for our patients with cardiac insufficiency.
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PMID:[Vasopressin antagonists]. 1193 60

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

Previous studies showed that aquaporin 2 (AQP2) is elevated in the kidney of the heart failure rat suggesting that an increased amount of AQP2 contributes to water retention in heart failure. We performed the present study to determine whether angiotensin II play a role in causing an increase in the expression of arginine vasopressin (AVP) V2 and AQP2 mRNA in the kidney of the cardiomyopathic hamster. The expression of AVP V2 and AQP2 mRNA in the inner medullary collecting duct (IMCD) was measured by competitive reverse transcriptase-polymerase chain reaction (RT-PCR) before and after treatment with an angiotensin-converting enzyme inhibitor, enalapril. Our results showed that the expression of AVP V2 (0.53 +/- 0.05 v 1.03 +/- 0.15 amol/microg of total RNA, P <.01) and AQP2 mRNA (0.027 +/- 0.002 v 0.036 +/- 0.002 amol/microg of total RNA, P <.05) in the IMCD of the cardiomyopathic hamster is upregulated. Treating the cardiomyopathic hamster with enalapril for 7 days negated the changes. In situ hybridization experiments confirmed the intensity of the signals for both AVP V2 and AQP2 mRNA was more intense in the IMCD of the cardiomyopathic hamster. Enalapril treatment reduced the signal intensity to a level comparable to the normal hamster. These results suggested that the increases in the expression of AVP V2 and AQP2 mRNA are mediated by angiotensin II.
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PMID:Upregulation of vasopressin V2 and aquaporin 2 in the inner medullary collecting duct of cardiomyopathic hamsters is attenuated by enalapril treatment. 1214 68

Circulating endothelin (ET) levels are elevated in heart failure and positively correlated with severity of heart failure. Recent studies demonstrated arginine vasopressin (AVP) V2 mRNA expression was upregulated in the inner medullary collecting duct (IMCD) of cardiomyopathic hamsters (CM). The goal of the present studies was to determine if ET-1 is involved in upregulating the expression of AVP V2 mRNA in the IMCD of CM by using a mixed ETA/ETB receptor antagonist bosentan. Our results showed plasma ET-1 levels increased in CM hamsters and related with the severity of heart failure. The competitive reverse-transcriptase polymerase chain reaction (RT-PCR) method was used to quantify the expression of AVP V2 and aquaporin 2 (AQP2) mRNA in the IMCD. AVP V2 mRNA expression was elevated in placebo-treated CM hamsters and decreased significantly with 14 days of bosentan treatment. Similar results were seen with AQP2 mRNA. The effect of bosentan in normalizing the expression of AVP V2 and AQP2 mRNA in the IMCD of CM was confirmed by in situ hybridization studies. Bosentan treatments reduced the intensitites of the signals in the IMCD of CM hamsters to that seen in normal hamsters. This study demonstrated that AVP V2 and AQP2 mRNA are upregulated in CM hamsters and these upregulations are attenuated by bosentan treatment, suggesting that ET-1 plays a role in upregulating the expression of AVP V2 mRNA in CM hamsters.
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PMID:Attenuation of renal vasopressin V2 receptor upregulation by bosentan, an ETA/ETB receptor antagonist. 1450 20

The pharmacology and pharmacokinetics of diuretics are unique among therapeutic drugs. Knowledge of these principles can be used to great advantage in the management of heart failure, whereas ignoring them can lead to either minor or life-threatening adverse consequences. Two major categories of potential therapeutic problems are diuretic resistance and the development of disturbances in serum potassium and other electrolytes. Inhibition of sodium reabsorption in the loop of Henle or distal convoluted tubule leads to renal potassium wasting, whereas inhibition of sodium reabsorption in the collecting duct (either directly, as with triamterene or amiloride, or through aldosterone antagonism) causes potassium retention. Combining diuretics of different classes, a rational and frequently used strategy to counter diuretic resistance, can be anticipated to balance or magnify these effects, depending on the site of action of the individual drugs.
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PMID:Rational diuretic management in congestive heart failure: a case-based review. 1471 90

Cells in the cortical collecting duct of distal nephron have been considered for a long time as the unique cellular targets of aldosterone. However, it is now clear that other cell types in non-epithelial tissues are also potential targets for aldosterone. The functions that this hormone controls in non-epithelial tissues are still a matter of debate. Clinical and experimental studies have established that aldosterone plays a major role in the pathophysiology of cardiovascular and renal diseases. The aldosterone receptor antagonists spironolactone and eplerenone have demonstrated specific effects not related to their hypotensive properties in hypertension or cardiac diseases. It appears that a key action of these molecules is related to prevention or treatment of end-organ damage. The latter fact, and the recognition of aldosterone escape on long-term treatment of heart failure, diabetic nephropathy and some forms of hypertension with ACE inhibitors, justify the clinical use of aldosterone receptor antagonists provided that kaliemia is controlled. Experimental studies have allowed to draw a still incomplete but comprehensive scheme of aldosterone cardiovascular actions in pathological conditions. When elevated, aldosterone has deleterious effects in blood vessels, in the heart and in kidney, which are secondary to the induction of inflammatory and oxidative processes and necrosis, that induce the increased synthesis of extracellular matrix proteins.
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PMID:Aldosterone and anti-aldosterone effects in cardiovascular diseases and diabetic nephropathy. 1552 73

The recrudescence of interest in manipulation of the arginine vasopressin system and especially of V2 vasopressin receptor blockade in heart failure stems from the limited efficacy and possible detrimental effects of loop diuretics. The "braking phenomenon," hypertrophy of the collecting duct cells, and altered pharmacodynamics contribute to loop diuretic resistance in heart failure. Selective (tolvaptan) and nonselective (conivaptan) V2 vasopressin receptor antagonists now known as "vaptans" promote free-water excretion that is labeled aquaresis and correct hyponatremia in patients with severe heart failure. A large mortality study with tolvaptan in heart failure is presently ongoing.
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PMID:Vasopressin antagonists in heart failure. 1603 44

Hyponatraemia is a common clinical finding in cardiac failure, complicating the management of these patients. Vasopressin plays a fundamental role in the physiopathology of the hyponatraemia of cardiac failure and binds to two distinct specific receptors, receptor V1a and V2. The V2 receptors, situated in the renal collecting duct, control the resorbtion of free water. The V1a receptors, present everywhere, are responsible for the vasoconstrictive effect of vasopressin. Specific antagonists of vasopressin receptors are being evaluated in pathologies associated with hyponatraemia. The preliminary results in patients with cardiac failure are encouraging and mortality studies are underway.
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PMID:[Hyponatraemia, antagonists of the antidiuretic hormone and cardiac failure]. 1661 24

This article discusses the pathophysiology of sodium and water retention in edematous disorders with a particular focus on cardiac failure, cirrhosis, and pregnancy. The body fluid volume hypothesis, which emphasizes the dominant role of arterial baroreceptors in renal sodium and water excretion, is reviewed. With arterial underfilling, either due to a decrease in cardiac output or peripheral arterial vasodilation, the normal central inhibition of the sympathetic nervous system activity and baroreceptor-mediated, nonosmotic arginine vasopressin (AVP) release is attenuated. The resultant increase in renal adrenergic activity stimulates the renin-angiotensin-aldosterone system. Although the resultant increase in systemic vascular resistance compensates for the primary arterial underfilling, this activation of the neurohumoral axis results in diminished sodium and water delivery to the renal collecting duct sites of aldosterone, AVP, and natriuretic peptide action. This diminished distal sodium and water delivery will be discussed as an important factor in the failure to escape from the sodium-retaining effects of aldosterone, the resistance to the natriuretic and diuretic effects of natriuretic peptides, and the diminished maximal solute-free water excretion in patients with edema. The role of the nonosmotic AVP release in water retention and hypo-osmolality/hyponatremia has been demonstrated in patients and experimental animals by administering nonpeptide, orally active vasopressin V2 receptor antagonists. These agents have been found to increase solute-free water excretion in patients with water-retaining, hyponatremic edema as well as in experimental animals.
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PMID:Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. 1684 85

Medullary sponge kidney was diagnosed in a 10-year-old male Shih Tzu dog with a long history of hyposthenuria, but with no other findings indicating renal failure or hormonal aberration. At the dog's death from heart failure, an autopsy was performed. On gross morphology, bilateral kidneys were normal size and had many cysts ranging from the corticomedullary junction to renal papillae. Histopathologic findings showed that almost all of the cysts were lined by monolayered or multilayered and columnar or cuboidal epithelium with chilium similar to epididymis. Immunohistochemically, all of these cells were strongly positive for AE1/AE3 and negative for vimentin. Many of these cells were positive for cytokeratin 7 (CK7), and only a few cells were positive for desmin. The results of staining are the same as those for epithelium of the collecting duct of normal canine kidney. This is the first report of this pathologic entity in the canine kidney.
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PMID:Medullary sponge kidney in a 10-year-old Shih Tzu dog. 1709 62


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