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)

Heart failure is characterized by sodium and fluid retention, sympathetic overactivity, parasympathetic withdrawal, vasoconstrictor activation and cytokine elevation. New therapies for heart failure attempt to control neurohormonal activation and limit progressive left ventricular dysfunction. Nesiritide (human B-type natriuretic peptide) is a recently approved new vasodilator that has been given to almost 1,000 patients in numerous clinical investigations; it belongs to a new class of heart failure drugs known as natriuretic peptides. Nesiritide decreases pulmonary capillary wedge pressure, systemic vascular resistance, mean right atrial pressure and pulmonary artery pressure, while improving cardiac index, stroke volume and heart failure symptoms. Many endothelin receptor antagonists are in various stages of development. Early clinical studies have demonstrated beneficial cardiovascular hemodynamic effects. Other new drugs for heart failure also include calcium sensitizers, neutral endopeptidase and vasopeptidase inhibitors, aldosterone receptor antagonists, vasopressin antagonists and cytokine inhibitors. All are being actively investigated and many show significant promise as beneficial therapies in the treatment of heart failure.
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PMID:New therapies for the treatment of congestive heart failure. 1253 83

In the renal collecting duct (CD) the major physiological role of aldosterone is to promote Na+ reabsorption. In addition, aldosterone may also influence CD water permeability elicited by vasopressin (AVP). We have previously shown that endogenous expression of the aquaporin-2 (AQP2) water channel in immortalized mouse cortical CD principal cells (mpkCCDC14) grown on filters is dramatically increased by administration of physiological concentrations of AVP. In the present study, we investigated the influence of aldosterone on AQP2 expression in mpkCCDC14 cells by RNase protection assay and Western blot analysis. Aldosterone reduced AQP2 mRNA and protein expression when administered together with AVP for short periods of time (< or =24 h). For longer periods of time, however, aldosterone increased AQP2 protein expression despite sustained low expression levels of AQP2 mRNA. Both events were dependent on mineralocorticoid receptor occupancy because they were both induced by a low concentration of aldosterone (10-9 m) and were abolished by the mineralocorticoid receptor antagonist canrenoate. Inhibition of lysosomal AQP2 protein degradation increased AQP2 protein expression in AVP-treated cells, an effect that was potentiated by aldosterone. Finally, both aldosterone and actinomycin D delayed AQP2 protein decay following AVP washout, but in a non-cumulative manner. Taken together, our data suggest that aldosterone tightly modulates AQP2 protein expression in cultured mpkCCDC14 cells by increasing AQP2 protein turnover while maintaining low levels of AQP2 mRNA expression.
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PMID:Dual influence of aldosterone on AQP2 expression in cultured renal collecting duct principal cells. 1266 Feb 45

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

Dehydration is a classic homeostatic stressor in rats that leads to a series of endocrine responses including stimulation of the hypothalamo-pituitary-adrenal (HPA) axis. During the last decade, it has been well established that perinatal food restriction is associated with the onset of diseases in adults. Our previous demonstration of long-term alterations in HPA axis activity in both basal conditions and after a 72-hour dehydration period in 4-month-old rats exposed to a 50% maternal food restriction (FR50) in late gestation and lactation prompted us to investigate whether such perinatal undernutrition further affects HPA axis activity in mature animals. As previously described in 4-month-old rats under basal conditions, 8-month-old FR50 rats showed reduced body weight and an enhanced ratio between mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA levels in the hippocampus, as well as increased pro-opiomelanocortin (POMC) mRNA levels in the adenohypophysis. In addition, numerous additional alterations appeared in mature rats. In the hypothalamus, levels of vasopressin (VP) mRNAs were increased both in the paraventricular nucleus (PVN) and in the supraoptic nucleus (SON). In the adenohypophysis, GR and prohormone-convertase 2 (PC2) mRNA levels were significantly increased, whereas prohormone-convertase 1 (PC1) mRNA was not affected by maternal undernutrition. Interestingly, undernourished animals exhibited high plasma levels of total and free corticosterone in spite of normal corticotropin (ACTH) levels, an indication that HPA basal activity is enhanced by maternal undernutrition in 8-month-old animals. Dehydration for 72 h induced a rise in ACTH plasma levels, but did not modify total and free corticosterone plasma levels in 8-month-old FR50 animals. In the adenopituitary, POMC mRNA levels were decreased after dehydration but PC1 mRNA levels were unaffected. The present study indicates that maternal food restriction during the perinatal period dramatically affects the activity of the HPA axis until the age of 8 months. We speculate that higher basal HPA activity and an inadequate HPA response after dehydration in mature animals may contribute to diseases such as hypertension, known to develop with aging in perinatally growth-restricted rats.
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PMID:Perinatal food deprivation induces marked alterations of the hypothalamo-pituitary-adrenal axis in 8-month-old male rats both under basal conditions and after a dehydration period. 1515 50

Diabetes is associated with increased basal hypothalamo-pituitary-adrenal (HPA) activity and impaired stress responsiveness. Previously, we demonstrated that the HPA response to hypoglycemia is significantly impaired in diabetic rats. In this study our goals were to 1) differentiate between the effects of hyperinsulinemia and those of hypoglycemia per se, and 2) establish whether diabetes lowers peak stress responses. Normal and streptozotocin-diabetic rats were subjected to hyperinsulinemic-euglycemic glucose clamps to evaluate central and peripheral responses. These were compared with peak ACTH and corticosterone responses to restraint and hypoglycemia. Hyperinsulinemia increased CRH and vasopressin mRNA, and plasma ACTH and corticosterone in normal and diabetic rats. In normal animals, insulin-induced activation of ACTH and corticosterone was lower than the responses during either restraint or hypoglycemia. In contrast, ACTH and corticosterone activation in diabetic rats was similar with all three stressors. Pituitary-adrenal axis activation in diabetic animals was also much lower compared with that in normal controls. The response to hyperinsulinemia (euglycemia) was associated with increases in glucocorticoid receptor mRNA in the anterior pituitary and paraventricular nucleus. Hippocampal mineralocorticoid receptor mRNA expression was increased in normal, but not in diabetic, animals. We speculate that the ability to appropriately match the HPA response to the potency of a stressor is related to the ability to alter hippocampal mineralocorticoid receptor expression. In diabetes, this ability is impaired; hence, maximal HPA activation is greatly diminished. This is a novel observation that may have important implications in the treatment of impaired counterregulatory mechanisms in human diabetes.
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PMID:Insulin alone increases hypothalamo-pituitary-adrenal activity, and diabetes lowers peak stress responses. 1556 37

Diuretics, ACE inhibitors and betablockers form the cornerstone of pharmacological treatment of chronic heart failure (CHF), while angiotensin receptor blockers are gaining ground. However, despite optimal treatment CHF remains a syndrome with poor prognosis. For this reason, a large number of new agents have been developed as add-on treatment over the last few years. Vasopeptidase inhibitors, moxonidine, endothelin antagonists, vasopressin antagonists, and selective aldosterone antagonists, are some of the new agents that were designed to interfere with different neurohormonal pathways. Immunomodulating agents, growth hormone, caspase inhibitors, adrenomedullin, and erythropoietin have different modes of action, which in general are less understood. Although most of the agents exhibited efficacy in preclinical trials, the clinical results have not always been similarly positive. The results of trials involving vasopeptidase inhibitors, endothelin antagonists, immunomodulating agents, and growth hormone have been disappointing. Other compounds like caspase inhibitors, adrenomedullin, and vasopressin antagonists are still at the early stages of development. Currently, the two most promising agents seem to be erythropoietin and the selective aldosterone receptor blocker eplerenone. In the present article an overview of new pharmacological developments for CHF is given, and the clinical value of these developments is discussed.
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PMID:New pharmacological strategies in chronic heart failure. 1577 Apr 37

The aim of this study was to evaluate the efficacy of agomelatine (S 20098) to accelerate reversal of the neuroendocrinological, behavioural and cyclical changes seen in a transgenic mouse model of the neuroendocrine characteristics of depression. The effects of agomelatine were assessed in transgenic mice with low glucocorticoid receptor (GR) function, after acute stress or induced phase shift, and compared to desipramine and melatonin. Mice were injected 2 h before the onset of the dark period with agomelatine (10 mg/kg, i.p.), desipramine (10 mg/kg, i.p.), melatonin (10 mg/kg, i.p.) or vehicle (hydroxy-ethyl-cellulose (HEC) 1%) each day for 21 to 42 days. Agomelatine was effective in reversing the transgenic mouse behavioural changes noted in the Porsolt forced swim test as well as in the elevated plus maze. Both the number of open arm entries and the total time spent in open arms of the elevated plus maze is greatly increased in transgenic mice. The mean time spent in open arms is exquisitely sensitive to reversal by agomelatine and desipramine. Agomelatine also markedly accelerated readjustment of circadian cycles of temperature and activity following an induced phase shift. This action of agomelatine was superior to that of melatonin while desipramine was without effect. The accelerating effect of agomelatine was particularly notable if treatment was started 3 weeks prior to the induced phase shift. Agomelatine treatment did not cause any major change in corticosterone or adrenocorticotropic hormone (ACTH) concentrations nor in vasopressin (AVP), corticotropin-releasing hormone (CRH), GR and mineralocorticoid receptor (MR) mRNAs levels, which make it unlikely that the mechanism of agomelatine action is related to hypothalamic-pituitary-adrenocortical (HPA) axis changes. The present study shows that agomelatine displays some characteristics of antidepressant drug action in the transgenic mouse model, effects that could be partially related to its chronobiotic properties.
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PMID:Antidepressant action of agomelatine (S 20098) in a transgenic mouse model. 1600 35

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

The kidney responds to high levels of ANG II, as may occur during malignant hypertension, by increasing sodium and water excretion. To study whether kidney medullary transporters contribute to this response, rats were made hypertensive using ANG II. Within 3 days of being given ANG II, systolic blood pressure (BP) was increased (200 mmHg), vs control (130 mmHg), and remained high through day 14. Kidney inner medullary (IM) tip and base and outer medulla were analyzed for transporter protein abundance. There were significant decreases in UT-A1 urea transporter, aquaporin-2 (AQP2) water channel, and NKCC2/BSC1 Na(+)-K(+)-2Cl(-) cotransporter. To determine whether the decreases were a response to hypertension, ANG II, or an ANG II-induced increase in aldosterone, rats were given 1) norepinephrine (to increase BP) and 2) ANG II plus spironolactone (to block the mineralocorticoid receptor). Norepinephrine (7 days) increased BP, urine volume, sodium excretion, and decreased urine osmolality and UT-A1, AQP2, and NKCC2/BSC1 abundances, similar to ANG II. ANG II alone or with spironolactone yielded similar increases in BP, urine volume, and urine osmolality, and decreases in UT-A1 and AQP2 proteins in the IM tip. Plasma vasopressin was unaffected by treatment. Water diuresis did not change UT-A1 but decreased AQP2 and NKCC2/BSC1 abundances. We conclude that decreases in UT-A1, AQP2, and NKCC2/BSC1 proteins may contribute to the diuresis and natriuresis that occur following ANG II or norepinephrine-induced acute hypertension and do not appear to involve ANG II stimulation of aldosterone or thirst.
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PMID:Urea transporter UT-A1 and aquaporin-2 proteins decrease in response to angiotensin II or norepinephrine-induced acute hypertension. 1678 41

The failing heart produces a variety of biologically active humoral factors such as catecholamines, vasopressin, angiotensin II, aldosterone, atrial natriuretic polypeptide (ANP), brain natriuretic polypeptide (BNP), cytokines and so on, in order to recover the cardiac function through the mechano- and chemo-receptors in vivo. In particular, it has recently shown that the central nervous system plays a pivotal role in the progression of cardiac remodeling and the heart failure. Thereby, endogenous digitalis-like factor, angiotensisn II, aldostereone, and inflammatory cytokines in the brain are acting as the mediators. In fact, mineralocorticoid receptor blockers, such as spironolactone and eplerenone, are clinically useful to treat cardiac failure. However, these biomarkers are not available as laboratory tests because they are under investigation clinically. On the other hand, failing heart by itself produces natriuretic hormones such as ANP and BNP to rescue it. They dilate resistant vessels to reduce the afterload of the heart with the lowest concentrations. Then, natriuresis is caused with the increased concentrations to reduce the pre-load to the heart. The natriuresis is brought partially by reducing concentrations of plasma aldosterone. Therefore, concentrations of these natriuretic hormones are excellent biomarkers for the cardiac function. They increase in a variety of disease states like hypertension, acute/old myocardial infarction, angina pectoris, arrhythmias, cardiac failure, cardiomyopathy, renal failure and myocarditis. In particular, they are remarkably increased in patients with heart failure. Recently, a new biomarker, N-terminal pro-BNP (NT-proBNP) is registered as a clinically available laboratory test, which may be superior to BNP at the laboratory stand of view. It is because NT proBNP is not degraded in the circulation, stable even in serum and the higher concentration as compared to BNP.
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PMID:[Pathophysiology of heart failure and the biomarkers; brain natriuretic hormone as the class-1 recommendation by the new Japanese Guideline for Heart Failure]. 1828 62


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