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)

1. Large concentrations (in mM) of ethacrynic acid (0.1), furosemide (1.0), theophylline (5.0) and osmotic diuretics (100.0) sharply increased the flux of water along an osmotic gradient through the frog urinary bladder wall. Spironolactone (0.1), and hydrochlorothiazide (5.0) showed only a weak action on osmotic permeability. MercusalR, clopamide and triamterene did not affect water transport. 2. The presence of 0.2--1.0 mU/ml vasopressin (ADH) after pretreatment with a diuretic did not result in summation of the effects of both drugs used. 0.01--0.1 mM ethacrynic acid and 0.01 mM MercusalR significantly decreased the reaction to ADH. 1.0 mM furosemide, 0.1 mM spironolactone, 0.01 mM clopamide and 0.8 mM acetazolamide did not change the reaction to ADH. A reduction in the cellular response to ADH and a decrease in the osmotic permeability of the tubular wall may be responsible in part for the diuretic action of ethacrynic acid and MercusalR.
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PMID:The effect of diuretics and vasopressin on the osmotic permeability of the frog urinary bladder. 13 27

Medical treatment of cirrhotic ascites is essentially supportive, dictated by the patient's discomfort, impaired cardiovascular or respiratory function and potential for infection. Treatment of 'simple' ascites (moderate fluid accumulation, serum albumin > 3.5 g/dl, serum creatinine < 1.5 mg/dl, no electrolyte disturbance) is implemented sequentially. Only 10% of patients respond to dietary sodium restriction and bed rest; most require pharmacotherapy consisting of spironolactone, which increases the proportion of responding patients to 65% and loop diuretics, which may produce clinical improvement in an additional 20% (85% in all); in the remaining 15% of refractory patients, use of novel adjunctive therapies may be attempted. Patients with tense ascites, impaired renal function and electrolyte disturbances merit special consideration before diuretics are introduced. Spironolactone has long been a standard for the treatment of cirrhotic ascites because it directly antagonizes aldosterone. The loop diuretic most frequently added to spironolactone has been furosemide. However, there is preliminary evidence that torasemide may be more effective in some patients. Other investigational agents that may play a role in treatment of patients resistant to conventional drugs include ornipressin (a vasopressin analogue) and atrial natriuretic factor.
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PMID:Medical treatment of ascites in cirrhosis. 849 70

The in-depth study of the pathophysiology of portal hypertension is the basis for a correct medical treatment. The backward-flow theory of portal hypertension stresses the importance of increased hepatic vascular resistance, while the forward-flow theory of portal hypertension underscores generalized vasodilation, the hyperdynamic circulation and increased portal inflow. The role of expanded plasma volume has been emphasized in recent studies. The aim of drug therapy is to normalize each one of these components. Vasoconstrictor agents, i.e. vasopressin, triglycyl-lysin-vasopressin, non selective beta-blockers, somatostatin and octreotide, try to normalize the increased portal inflow and to decrease porto-collateral blood flow. Venous vasodilators, e.g. nitrates, mainly act by decreasing portal blood outflow resistance. Spironolactone has been proposed to decrease plasma volume. The use of a combination of a vasoconstrictor agent and a vasodilator or spironolactone has been proposed to increase the efficacy of medical treatment.
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PMID:[Physiopathologic basis of medical therapy of portal hypertension in cirrhosis]. 900 19

Ascites accumulation is the product of a complex process involving hepatic, renal, systemic, hemodynamic, and neurohormonal factors. The main pathophysiologic theories of ascites formation include the "underfill," "overflow," and peripheral arterial vasodilation hypotheses. These theories are not necessarily mutually exclusive and are linked at some level by a common pathophysiologic thread: The body senses a decreased effective arterial blood volume, leading to stimulation of the sympathetic nervous system, arginine-vasopressin feedback loops, and the renin-angiotensin-aldosterone system. Cornerstones of ascites management include dietary sodium restriction and diuretics. Spironolactone is generally tried initially, with furosemide added if clinical response is suboptimal. More refractory patients require large-volume paracentesis (LVP) accompanied by volume expansion with albumin. Placement of a transjugular intrahepatic portosystemic shunt is reserved for individuals with compensated liver function who require very frequent sessions of LVP. Peritoneovenous shunts are not used in contemporary ascites management. Liver transplantation remains the definitive therapy for refractory ascites. Although treatment of ascites fails to improve survival, it benefits quality of life and limits the development of such complications as spontaneous bacterial peritonitis.
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PMID:Pathophysiology and management of pediatric ascites. 1273 47

Adrenalectomy in rats is associated with urinary concentrating and diluting defects. This study tested the effect of adrenal steroids on the UT-A1 urea transporter because it is involved in the urine-concentrating mechanism. Rats were adrenalectomized and given normal saline for 14 d, after which they received (1) vehicle, (2) aldosterone, or (3) spironolactone plus aldosterone. Adrenalectomy alone significantly increased UT-A1 protein in the inner medullary tip after 7 d, whereas aldosterone repletion reversed the effect. Spironolactone blocked the aldosterone-induced decrease in UT-A1, indicating that aldosterone was working via the mineralocorticoid receptor. For verifying that glucocorticoids downregulate UT-A1 protein through a different receptor, three groups of adrenalectomized rats were prepared: (1) vehicle, (2) adrenalectomy plus dexamethasone, and (3) adrenalectomy plus dexamethasone and spironolactone. Dexamethasone significantly reversed UT-A1 protein abundance increase in the inner medullary tip of adrenalectomized rats. When spironolactone was given with dexamethasone, it did not affect the dexamethasone-induced decrease in UT-A1. There was no significant change in serum vasopressin level, aquaporin 2, or Na(+)-K(+)-2Cl(-) co-transporter NKCC2/BSC1 protein abundances or UT-A1 mRNA abundance in any of the groups. In conclusion, either mineralocorticoids or glucocorticoids can downregulate UT-A1 protein. The decrease in UT-A1 does not require both steroid hormones, and each works through a different receptor.
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PMID:Aldosterone decreases UT-A1 urea transporter expression via the mineralocorticoid receptor. 1497 57

Vasopressin and aldosterone are essential hormones in the regulation of water and sodium balance. Aldosterone regulates sodium reabsorption, although synergistic effects on collecting duct water permeability have been shown. We investigated the effects of 7-day aldosterone infusion or oral spironolactone treatment on water balance and aquaporin (AQP) 2 expression in rats with 21 days of lithium-induced nephrogenic diabetes insipidus (Li-NDI). In rats with Li-NDI, aldosterone markedly increased (271 +/- 14 ml/24 h), whereas spironolactone decreased (74 +/- 11 ml/24 h) urine production compared with rats treated with lithium only (120 +/- 11 ml/24 h). Aldosterone increased free-water clearance and creatinine clearance, whereas spironolactone caused a decreased creatinine clearance but unchanged free-water clearance. Immunoblotting showed unchanged AQP2 expression in cortex/outer stripe of the outer medulla and inner medulla. In the inner stripe of the outer medulla aldosterone caused a decreased AQP2 expression, whereas spironolactone caused an increase compared with rats treated with lithium only. Semiquantitative confocal immunofluorescence microscopy of AQP2 immunolabeling showed reduced AQP2 expression in the apical plasma membrane domain in connecting tubule (CNT) and initial cortical collecting ducts (iCCD) in response to aldosterone-treated rats compared with rats treated with lithium only. Spironolactone significantly increased apical AQP2 expression in the iCCD compared with rats treated with lithium only. We also tested whether similar changes could be observed in vasopressin-deficient BB rats and found similar changes in urine production and subcellular AQP2 expression in the CNT and iCCD in response to aldosterone and spironolactone. This study shows that aldosterone treatment perturbs diabetes insipidus and is associated with AQP2 redistribution in CNT and iCCD likely mediated by the spironolactone-sensitive mineralocorticoid receptor.
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PMID:Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus. 1615 98

Lithium-induced nephrogenic diabetes insipidus (Li-NDI) is associated with increased urinary sodium excretion and decreased responsiveness to aldosterone and vasopressin. Dysregulation of the epithelial sodium channel (ENaC) is thought to play an important role in renal sodium wasting. The effect of 7-day aldosterone and spironolactone treatment on regulation of ENaC in rat kidney cortex was investigated in rats with 3 wk of Li-NDI. Aldosterone treatment of rats with Li-NDI decreased fractional excretion of sodium (0.83 +/- 0.02), whereas spironolactone did not change fractional excretion of sodium (1.10 +/- 0.11) compared with rats treated with lithium alone (1.11 +/- 0.05). Plasma lithium concentration was decreased by aldosterone (0.31 +/- 0.03 mmol/l) but unchanged with spironolactone (0.84 +/- 0.18 mmol/l) compared with rats treated with lithium alone (0.54 +/- 0.04 mmol/l). Immunoblotting showed increased protein expression of alpha-ENaC, the 70-kDa form of gamma-ENaC, and the Na-Cl cotransporter (NCC) in kidney cortex in aldosterone-treated rats, whereas spironolactone decreased alpha-ENaC and NCC compared with control rats treated with lithium alone. Immunohistochemistry confirmed increased expression of alpha-ENaC in the late distal convoluted tubule and connecting tubule and also revealed increased apical targeting of all three ENaC subunits (alpha, beta, and gamma) in aldosterone-treated rats compared with rats treated with lithium alone. Aldosterone did not, however, affect alpha-ENaC expression in the cortical collecting duct (CCD), which showed weak and dispersed labeling similar to that in rats treated with lithium alone. Spironolactone did not affect ENaC targeting compared with rats treated with lithium alone. This study shows a segment specific lack of aldosterone-mediated alpha-ENaC regulation in the CCD affecting both alpha-ENaC protein expression and trafficking, which may explain the increased sodium wasting associated with chronic lithium treatment.
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PMID:Lithium-induced NDI in rats is associated with loss of alpha-ENaC regulation by aldosterone in CCD. 1633 30

Ascites, the most common complication of cirrhosis, is associated with a poor quality of life, an increased risk of infection, and renal failure. Twenty percent of cirrhotic patients have ascites at the time of diagnosis, while 30% and 50% will develop ascites by 5 and 10 years, respectively. There are several factors that contribute to ascites formation in cirrhotic patients, these include splanchnic vasodilatation, arterial hypotension, high cardiac output, and decreased vascular resistance. These factors lead to ineffective intravascular volume (hyperdynamic state), impairment of renal function, and subsequent water and sodium retention, all of which lead to dilutional hyponatremia (serum sodium <130 mEq/L), one of the most important prognostic factors in these patients. In conclusion, the therapeutic objective is to improve sodium balance and circulatory function through non-pharmacological measures, such as dietary sodium and water restriction as well as bed rest. Spironolactone (100-400 mg/day) is the initial drug of choice, while loop diuretics (like furosemide, 40-60 mg/day) are frequently used as adjuvants. Recently, agent that interfere with the renal effects of vasopressin by inhibiting water reabsorption in collecting ducts and producing free water diuresis have been used. These agents are called aquaretics and can be useful in the treatment o ascites unresponsive to conventional therapy.<br />
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PMID:Pathophysiology of ascites and dilutional hyponatremia: contemporary use of aquaretic agents. 1800 50

Background: The exact pathophysiological mechanism(s) underlying endolymphatic hydrops (EH) remain elusive. We have previously shown that chronic administration of vasopressin and inhibitors of the cAMP/cGMP degrading enzymes (PDE3, PDE4, PDE5) results in the development of EH to mice. Aims/objectives: Evaluate the ability of spironolactone, an aldosterone antagonist, to prevent EH, when induced by different pathways. Material and methods: Mice were treated for 4 weeks with vasopressin, the PDE3 inhibitor cilostamide and the PDE4 inhibitor rolipram in the presence or absence of spironolactone. EH was assessed using high resolution 9.4T MRI. The expression of proteins in human saccule sensory epithelium was studied with immunohistochemistry. Results: Spironolactone prevents EH induced by vasopressin and rolipram, but not hydrops induced by cilostamide. The aldosterone target ENaC and the mineralocorticoid receptor were expressed in the human saccule sensory epithelium. Conclusions: The effect of spironolactone on EH appears to be pathway-dependent and may provide explanations why certain drugs may be effective in some patients with hydropic ear disease while not in others. Significance: Extrapolating this finding to the clinic supports that a personalized medicine approach is probably necessary in the treatment of diseases involving EH, as different pathways may be needed to be targeted for treatment.
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PMID:Endolymphatic hydrops induced by different mechanisms responds differentially to spironolactone: a rationale for understanding the diversity of treatment responses in hydropic inner ear disease. 3114 14