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 aim of the present study was to determine whether a severely Mg-deficient diet can modify blood pressure in rats and whether these alterations in blood pressure are associated with a change in in vivo cardiovascular reactivity, alteration in plasma lipids and modification of the production of hormones involved in blood pressure regulation. Weanling male Wistar rats were pair-fed for 40 weeks with control (960 mg Mg/kg) and Mg-deficient (80 mg Mg/kg) diets. At 2 weeks, blood pressure was lower in Mg-deficient rats, while heart rate was greater than in controls. Mg-deficiency-induced hypotension was transitory and the administration of antihistamine agents inhibited the appearance of this hypotensive phase, suggesting that histamine may play a role in lowering blood pressure. Until 15 weeks, blood pressures were similar for control and Mg-deficient rats. Thereafter, blood pressure rose gradually until the end of the experiment in Mg-deficient rats. Heart rate remained higher in hypertensive Mg-deficient rats. After 21 weeks, in vivo cardiovascular reactivity to noradrenaline was lower and reactivity to angiotensin II was unchanged in hypertensive Mg-deficient rats. At 2 and 21 weeks, hypomagnesaemia was accompanied by higher plasma levels of Ca, triacylglycerols and cholesterol. Plasma renin activity was higher at week 2, whereas levels of plasma angiotensin converting enzyme were lower at 2 and 21 weeks in Mg-deficient rats. The plasma aldosterone level was higher at 2 and 21 weeks while the vasopressin level did not change. Plasma corticosterone levels were lower at 2 weeks and higher at 21 weeks. It is concluded that Mg deficiency induced a transitory hypotension followed by a sustained hypertension in rats. The release of vasodilator inflammatory agents may contribute to the early hypotension. The hypertensive phase may be explained by the increased sympathetic nervous activity induced by Mg deficiency even though the contribution of several hormonal systems implicated in blood pressure regulation remains to be elucidated.
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PMID:Time-course of the change in blood pressure level in magnesium-deficient Wistar rats. 1065 71

Cardiac pump failure leads to a reduction of the effective arterial volume. This is sensed by the kidney via afferent sympathetic fibres. The renal response to the perceived lack of volume is the retention of sodium and water. Although initially homeostatic, this renal counterregulation is maladaptive later on and may contribute to further cardiac compromise by increasing preload (volume retention) and afterload (hyperreninism). The renal sodium retention in congestive heart failure is a consequence of the activation of the sympathetic nervous system and of the renin-angiotensin-aldosterone system. The retention of osmotically free water is partly caused by the nonosmotic secretion of antidiuretic hormone from the posterior pituitary and partly by a diminished osmoregulatory capacity of the kidney due to diuretic therapy and/or (pre-)renal insufficiency. In the near future specific blocking drugs of vasopressin receptors should become available which could make a significant contribution to the management of hyponatremia in this setting. For the management of extracellular volume overload a negative sodium balance is the central objective. A moderate reduction of sodium intake is helpful to achieve this goal and has the additional benefit of reducing thirst and renal potassium loss. However, the majority of patients require (loop) diuretics in addition. Patients who are refractory to high and repeated doses of loop diuretics may respond to a combination of diuretics which act on different nephron segments. Diuretics increase the risk of hypokalemia which can trigger life-threatening tachyarrhythmia, particularly in patients with cardiac dysfunction. Hypokalemia is therefore an indicator of an adverse outcome. Secondary hyperaldosteronism--which can persist despite effective therapy with ACE-inhibitors--is the major cause of hypokalemia in this setting. The randomized aldactone evaluation study (RALES) has shown that spironolactone (25 mg/day) reduced the risk of hypokalemia and decreased morbidity, mortality and clinical symptoms in patients with heart failure. The recent encouraging results with vasopressin receptor antagonists and spironolactone point to the fact that the therapeutic modification of maladaptive homeostatic renal mechanisms plays an increasingly important role in the modern diuretic management of heart failure beyond symptomatic relief from volume overload.
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PMID:[Diuretic therapy in congestive heart failure--new views on spironolactone therapy]. 1089 22

The amino acid, taurine, is an important nutrient found in very high concentration in excitable tissue. Cellular depletion of taurine has been linked to developmental defects, retinal damage, immunodeficiency, impaired cellular growth and the development of a cardiomyopathy. These findings have encouraged the use of taurine in infant formula, nutritional supplements and energy promoting drinks. Nonetheless, the use of taurine as a drug to treat specific diseases has been limited. One disease that responds favorably to taurine therapy is congestive heart failure. In this review, we discuss three mechanisms that might underlie the beneficial effect of taurine in heart failure. First, taurine promotes natriuresis and diuresis, presumably through its osmoregulatory activity in the kidney, its modulation of atrial natriuretic factor secretion and its putative regulation of vasopressin release. However, it remains to be determined whether taurine treatment promotes salt and water excretion in humans with heart failure. Second, taurine mediates a modest positive inotropic effect by regulating [Na+]i and Na+/Ca2+ exchanger flux. Although this effect of taurine has not been examined in human tissue, it is significant that it bypasses the major calcium transport defects found in the failing human heart. Third, taurine attenuates the actions of angiotensin II on Ca2+ transport, protein synthesis and angiotensin II signaling. Through this mechanism taurine would be expected to minimize many of the adverse actions of angiotensin II, including the induction of cardiac hypertrophy, volume overload and myocardial remodeling. Since the ACE inhibitors are the mainstay in the treatment of congestive heart failure, this action of taurine is probably very important.
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PMID:Interaction between the actions of taurine and angiotensin II. 1094 14

The important neuroendocrine systems implicated in heart failure are reviewed here, with special emphasis on their possible role in pathophysiology and the chances of pharmacological intervention. The part played by the sympathetic nervous system and the renin-angiotensin-aldosterone system and the beneficial effects of beta-blockers, ACE inhibitors, and angiotensin II antagonists are well-established. The involvement of vasopressin, endothelin-1, ANP, BNP, and TNF-alpha and the interventional possibilities relating to these hormones are also discussed. It is concluded that, in addition to the known interventional principles of neuroendocrine activation, there is a series of new exciting principles and some of them might become important in the future.
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PMID:[Neuroendocrine activation in heart failure I. Pathophysiology and pharmacological intervention]. 1109 49

Requirements for an effective animal model of cognition are discussed with special reference to the cholinergic hypothesis of Alzheimer's disease. It is argued, with reference to research on vasopressin and ACE inhibitors, that many putative animal models of cognition lack predictive clinical validity because they either confound the effects of cognitive and arousal processes, or fail to model a specific component of cognitive functioning. A survey of recent research on the cholinergic hypothesis illustrates how these weaknesses can be overcome. Studies involving scopolamine and basal forebrain excitatory amino acid lesion models of the cholinergic deficit in Alzheimer's disease have employed a delayed-matching-to-position test in rodents which, unlike passive avoidance, allows the effects of memory and attentional variables to be distinguished. In combination with recent human studies, these experiments suggest that the cholinergic system has a major role in executive control of attentional resources, and lead to the recommendation of a 'top down' strategy in the investigation of neurochemical processes and pharmacological mechanisms underlying cognition.
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PMID:Pharmacological mechanisms and animal models of cognition. 1122 29

The management of heart failure has evolved in parallel with advances in the understanding of the disease process. Inotropes and diuretics are used to combat pump failure and fluid overload. While no convincing data has emerged regarding the long-term safety of inotropes, new exciting data concerning the role of diuretics, especially aldactone, has led to a renewed interest in this class of drug therapy. Angiotensin converting enzyme inhibitors (ACE inhibitors) were noted to not only affect symptomatology but also decrease mortality by interfering with the renin-angiotensin-aldosterone system. Recent research has focused on more complete blockade of the renin-angiotensin system than that achieved with ACE inhibitors alone with the addition of direct angiotensin II receptor blockers. This new class of drugs may become not only a reasonable alternative to ACE inhibitors in patients intolerant of the drug but also a possible addition to ACE inhibitors in the battle to prevent progression of remodelling and disease. beta-blockers are the most exciting new class of drugs used to combat heart failure. They appear not only to combat the remodelling process that occurs in the progression of disease but also other pathological events such as apoptosis and cellular oxidation. New medical therapies currently being investigated include novel agents such as endothelin antagonists, natriuretic peptides, vasopressin antagonists and anticytokine agents--all part of a new era in drug management of heart failure that has evolved with continued advances in the understanding of chronic heart failure (CHF).
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PMID:New advances in the pharmacological management of chronic heart failure. 1124 47

The important neuroendocrine systems involved in heart failure are reviewed with special emphasis on their possible role in pathophysiology and their relation to prognostic and diagnostic information. Plasma levels of noradrenaline (NA), renin, vasopressin, endothelin-1, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and tumour necrosis factor-alpha (TNF-alpha) are all elevated in heart failure. Activity of the sympathetic nervous system as reflected by NA is correlated to mortality and seems to possess independent prognostic information. Several studies have now documented the beneficial effect of beta-blockade in chronic heart failure (CHF). Renin seems to be a poor prognostic marker in CHF possibly because of the interference with diuretic treatment, angiotensin converting enzyme (ACE)-inhibitors and angiotensin II antagonist, and probably also because of the significance of tissue renin-angiotensin system (RAS), poorly reflected by plasma renin. On the other hand, several large-scale trials with ACE-inhibitors and angiotensin II antagonists have demonstrated reduced mortality and morbidity in CHF. Plasma vasopressin does not seem to possess prognostic information but testing of non-peptide antagonists is ongoing. Endothelin-1 seems to have independent prognostic information and endothelin receptor antagonists may represent a therapeutic possibility. The natriuretic peptides ANP and BNP are correlated to prognosis and possess independent information. Brain natriuretic peptide and N-terminal ANP seem to increase early, i.e. in asymptomatic heart failure. Plasma BNP being more stable than ANP is therefore a promising measure of left ventricular dysfunction. Increase in ANP and BNP, potentially beneficial, may be achieved by administration of neutral endopeptidase inhibitors, at present an unsettled therapeutic possibility. Several cytokines are increased in heart failure and especially TNF-alpha has drawn attention. Experimental studies suggest that TNF-alpha is important in the pathophysiology of heart failure and preliminary studies indicate that inhibition of TNF-alpha seems to be a possible therapeutic approach. Thus, neuroendocrine markers seem to (i) have a role in diagnosis and classification of heart failure, (ii) be useful in providing a 'neuroendocrine profile' which enlightens different aspects of heart failure, and therefore (iii) in the future probably will be valuable in the choice of medical treatment of the individual patient. In addition to beta-blockers, ACE-inhibitors and angiotensin II antagonists several new drugs based on neuroendocrine modification are on their way and might become important in the future.
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PMID:Heart failure and neuroendocrine activation: diagnostic, prognostic and therapeutic perspectives. 1172 73

Is heart failure an endocrine disease? Historically, congestive heart failure (CHF) has often been regarded as a mechanical and haemodynamic condition. However, there is now strong evidence that the activation of neuroendocrine systems, like the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, as well as the activation of natriuretic peptides, endothelin and vasopressin, play key roles in the progression of CHF. In this context, agents targeting neurohormones offer a highly rational approach to CHF management, with ACE inhibitors, aldosterone antagonists and beta-adrenergic blockade improving the prognosis for many patients. Although relevant improvements in clinical status and survival can be achieved with these drug classes, mortality rates for patients with CHF are still very high. Moreover, most patients do not receive these proven life-prolonging drugs, partially due to fear of adverse events, such as hypotension (with ACE inhibitors), gynaecomastia (with spironolactone) and fatigue (with beta-blockers). New agents that combine efficacy with better tolerability are therefore needed. The angiotensin II type 1 (AT(1))-receptor blockers have the potential to fulfil both these requirements, by blocking the deleterious cardiovascular and haemodynamic effects of angiotensin II while offering placebo-like tolerability. As shown with candesartan, AT(1)-receptor blockers also modulate the levels of other neurohormones, including aldosterone and atrial natriuretic peptide (ANP). Combined with its tight, long-lasting binding to AT(1)-receptors, this characteristic gives candesartan the potential for complete blockade of the RAAS-neurohormonal axis, along with the great potential to improve clinical outcomes.
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PMID:Neurohumoral blockade in CHF management. 1196 92

During the last years, the results of several trials on heart failure treatment were published or presented at international meetings. The new perspectives concern drug therapy and non-pharmacological strategies, such as cardioverter-defibrillators, biventricular resynchronization and implantable assist devices. Trials on beta-blockers extended the indication to patients with advanced heart failure, but the choice of the "best" beta-blocker to use remains an unsolved issue. Moreover, the concomitant use of ACE-inhibitors and angiotensin II receptor antagonists is a recent acquisition. However, the Val-HeFT results underscored that the add-on hypothesis of a more complete inhibition obtained with the combination of multiple agents was not confirmed in patients already taking ACE-inhibitors and beta-blockers. Regarding the new neurohormonal modulators (omapatrilat, etanercept, endothelin receptor blockers, arginine-vasopressin antagonists), more data are needed before using them in clinical practice. After the publication of the MADIT-II results, the cardioverter-defibrillator implantation will probably spread in patients with previous myocardial infarction and left ventricular dysfunction to prevent sudden death, but the cost-effectiveness ratio is still to be clarified. In the advanced or end-stage heart failure, when the improvement of quality of life represents the main target of therapy, ventricular resynchronization and implantable assist devices may play a role in clinical settings. Before considering them like a real therapeutic option, final results from ongoing investigations should be awaited.
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PMID:[Treatment of heart failure: an update]. 1218 29

Chronic heart failure (HF) will be the disease of the new millennium. The last decade has seen major developments in the management of HF, with beta-blockers and ACE inhibitors becoming the cornerstones of therapy by virtue of the reductions in total mortality. However, significant gaps remain. Hospitalization for exacerbations of HF are frequent and account for more than 6 million hospital days from this disease related group. Although a variety of intravenous (IV) agents are available for the management of exacerbations of HF, readmission rates are as high as 20%-47% at 6 months. Acute IV therapy for acute decompensation of chronic HF consists of inotropic agents most of which also have vasodilator properties, vasodilator, and diuretics. In addition, there are newer agents in various developmental stages, especially, calcium sensitizing drugs, vasopressin receptor antagonists, and natriuretic peptides. Despite the multiplicity of agents, there are no well designed, randomized, placebo controlled trials to guide IV inpatient therapy for HF exacerbations. (c)1999 by CHF, Inc.
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PMID:Intravenous therapy for chronic heart failure exacerbations. 1218 1


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