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)

Circulating plasma concentrations of norepinephrine, renin, angiotensin and vasopressin are increased in congestive heart failure. By increasing ventricular afterload, heart failure is further worsened, which in turn--in a vicious cycle--stimulates neurohumoral vasoconstrictor mechanisms. Furthermore, because of the compensatory but excessive stimulation of the sympathomimetic system, a down-regulation and desensitization particularly of the myocardial beta 1 receptors and depletion of myocardial catecholamine occurs in chronic heart failure. These defects may be restored toward normal by interventions that attenuate the activity of the sympathetic nervous system. A direct approach to modify the excessive vasoconstriction is to administer systemic vasodilator drugs, but despite favorable short-term effects, tolerance developed to most of these drugs during long-term treatment. One reason for the loss of effectiveness is the reflex activation of the sympathetic system, which increases vasoconstrictor hormone concentrations. Activation of the renin-angiotensin system can be modified effectively by angiotensin-converting enzyme inhibitors that have shown favorable responses in patients with chronic heart failure. Beta-blocking agents interfere with endogenous sympathetic activation and have produced beneficial effects in patients with congestive cardiomyopathy. Long-term treatment is associated with up-regulation of the number of beta receptors and an improved responsiveness to catecholamines. Owing to the negative inotropic effects of beta-blocking agents, some of the patients with severe heart failure deteriorated hemodynamically and clinically. Theoretically, it should be advantageous to have a substance that combines protection against excessive beta stimulation with a mild inotropic support to prevent cardiac decompensation. This may be achieved by a selective beta 1-partial agonist like xamoterol.
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PMID:Interrupting the adaptive changes in congestive heart failure. 167 86

The benzimidazol analogue BM14.478 is a phosphodiesterase inhibitor with both vasodilator and positive inotropic properties. Hemodynamic parameters and plasma hormone levels of 8 patients (1 female, 7 male) with chronic congestive heart failure NYHA Classes II-IV (1 patient with coronary artery disease, 7 patients with primary dilated cardiomyopathy) were assessed before and until 6 h after the intravenous application of 1.0 mg BM14.478. There was a significant decrease of mean pulmonary artery pressure (28 +/- 11 vs. 23 +/- 11 mmHg; p less than 0.05), mean right atrial pressure (8.6 +/- 5.2 vs. 5.0 +/- 4.7 mmHg; p less than 0.02), and systemic vascular resistance (1651 +/- 484 vs. 1206 +/- 252 dynes.s.cm-5; p less than 0.05) as early as 10 min after injection of BM14.478. Pulmonary vascular resistance also was reduced (128 +/- 86 vs. 61 +/- 39 dynes.s.cm-5, 30 min after injection; p less than 0.02). Simultaneously there was a significant increase of cardiac index (2.3 +/- 0.7 vs. 3.1 +/- 0.8 l.min-1.m-2, 10 min after injection; p less than 0.02), and stroke volume index (28.8 +/- 11.7 vs. 33.9 +/- 8.5 ml.min-1.m-2; 30 min after injection; p less than 0.05). Although mean heart rate did not change significantly, some patients reacted with a transient increase. There was also a slight but insignificant increase of the double product. No serious side effects were observed. The hemodynamic improvement was followed by a delayed reduction of plasma levels of epinephrine (51 +/- 20 vs. 41 +/- 21 pg/ml; p less than 0.02; 30 min after injection) and atrial natriuretic peptide (229 +/- 283 vs. 121 +/- 168 pg/ml; p less than 0.05; 1 h after injection). Mean levels of plasma norepinephrine, however, did not change significantly and individual responses showed large variations, which could not be predicted by the behavior of the hemodynamic parameters. Three of eight patients (2 of these with elevated baseline filling pressures) even showed a marked increase of plasma norepinephrine levels after BM14.478. Response of plasma renin activity and plasma vasopressin levels to BM14.478 also was heterogeneous. According to the results of this study, acute administration of the phosphodiesterase inhibitor BM14.478 has an immediate beneficial hemodynamic effect in patients with severe congestive heart failure by reducing both preload and afterload, and by increasing cardiac index and stroke volume. However, this improvement of hemodynamic parameters is not necessarily accompanied by a favorable short-term response of plasma hormones, and therefore does not allow any conclusions on survival of these patients.
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PMID:Hemodynamic and neuroendocrine response to acute administration of the phosphodiesterase inhibitor BM14.478 in patients with congestive heart failure. 204 89

A decrease in cardiac output in patients with congestive heart failure due to dilated cardiomyopathy is compensated by stimulation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. The increase in plasma norepinephrine and depletion of norepinephrine in the myocardium as well as the disturbance of beta-adrenal and baroreceptor function reflect the limits of the sympathetic nervous stimulation. Together with augmented levels of angiotensin II and vasopressin, this stimulation leads to a significant increase in systemic vascular resistance. Sustained stimulation of at least one of these mechanisms can cause further impairment of the left ventricular function. The severity and prognosis of congestive heart failure due to dilated cardiomyopathy is expressed by the plasma norepinephrine concentration and by its myocardial depletion. Ultimately, activation of the compensatory mechanisms provides the basis for therapeutic approaches: 1. reduction of afterload and systemic vascular resistance and/or 2. diminution of the sympathetic nervous activity. For about the last ten years, ACE inhibitors have been used as pharmacological treatment in addition to positive inotropic and vasodilating substances. Captopril, one of the first orally applicable drugs, reduces left ventricular filling pressure, pulmonary capillary pressure, systemic vascular resistance and increases the cardiac output. Beside the hemodynamic improvement, a decrease in plasma norepinephrine and aldosterone can be observed. Vasodilators and alpha-blocking agents can also reduce afterload and systemic vascular resistance in patients with congestive heart failure due to dilated cardiomyopathy, and may lead to hemodynamic improvement. The main limitations of their long-term application are relatively short duration of action, reflex activation of the renin-angiotensin system due to vasodilation and induction of tolerance.
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PMID:[Sympathetic activity in patients with heart failure due to idiopathic dilated cardiomyopathy: effect of ACE inhibitors and other vasodilators]. 219 17

The characteristics of norepinephrine and epinephrine as well as plasma renin activity, angiotensin II, aldosterone, vasopressin, and atrial natriuretic factor (ANF) were examined in 64 patients (mean age of 52 +/- 16 years) with dilated cardiomyopathy. The findings were grouped according to the NYHA classification and compared with a normal cohort of 38 patients (mean age of 42 +/- 10 years). Furthermore, the influence of different cardioactive substances used in the treatment of cardiac failure was analyzed in more detail. Patients in NYHA class II already demonstrated an increased activity of the sympathicoadrenal, renin-angiotensin-aldosterone system (RAAS), vasopressin, and ANF system. The highest values were found in patients of NYHA class IV. In these patients, norepinephrine was enhanced by a factor of 7, epinephrine by a factor of 2, plasma renin activity by a factor of 7, angiotensin II by a factor of 2.5, aldosterone by a factor of 5, vasopressin by a factor of 1.5, and ANF by a factor of 4 compared with those in normal subjects. The highest correlation coefficient was found for norepinephrine (r = 0.84). The acute application of 1-2 mg/kg of body weight of enoximone in patients with dilated cardiomyopathy (n = 15) resulted only in a significant lowering of the atrial natriuretic factor as an indicator for drug-induced unloading effects (venous pooling). All the parameters showed only a tendency; in none could statistical significance be established. Application of 0.75 mg/kg of body weight of enoximone i.v. in patients with coronary artery disease (n = 17) has no direct influence either on the sympathoadrenal, the ANF, or the prostaglandin systems. It could be demonstrated that the mode of medical treatment influences the parameters of vasoconstrictor systems in different ways.
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PMID:The influence of various degrees of cardiac failure, chronic medical treatment, and acute additional enoximone application on the parameters of the vasopressor system. 248 Apr 85

Alterations in the vasopressor system found in cardiac failure are part of compensatory measures that may modify pharmacologic-therapeutic response. Therefore, in 64 patients with dilated cardiomyopathy, we investigated its enhanced activity in different clinical stages of the disease as compared to normal controls. Patients in NYHA class II (n = 20) demonstrated increased activity of the sympathico-adrenal, renin-angiotensin-aldosterone, vasopressin, and atrial natriuretic factor systems, while maximum values were found in patients of NYHA class IV (n = 24). In these patients, noradrenaline was enhanced by a factor of 7, adrenaline by a factor of 2, plasma-renin-activity by a factor of 7, angiotensin II by a factor of 2.5, aldosterone by a factor of 5, vasopressin by a factor of 1.5, and ANF by a factor of 4 as compared to normal controls. Clinical NYHA classes correlated to a certain degree with the various plasma hormones. Patients treated with an aldosterone inhibitor in addition to digitalis and diuretics revealed significantly higher values for aldosterone, vasopressin, and angiotensin II as compared to those who received digitalis and diuretics alone. The addition of ACE-inhibitor therapy resulted in a decrease of angiotensin II, aldosterone, and vasopressin. Plasma catecholamines and ANF, however, did not change under the influence of cardiac medication. Diuretic treatment in NYHA class II patients reduced plasma volumes (p less than 0.01). Plasma volume in NYHA class IV patients only was found to be higher than in normal controls. Thus, analysis of the neurohumoral system can aid both in the identification of the clinical degree of dilated cardiomyopathy and in its optimal therapy.
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PMID:The vasopressor system in patients with heart failure due to idiopathic dilated cardiomyopathy--influence of the clinical stage of disease and of chronic drug treatment. 253 2

A 47-year-old man, with dilated cardiomyopathy developed severe hyponatremia and hypoosmolarity during captopril therapy. He also had an inappropriate elevation of antidiuretic hormone and urine osmolarity, but no evidence of dehydration, renal or suprarenal disturbances. The hyponatremia and hypoosmolarity improved after withdrawal of captopril alone, and recurred after readministration of captopril. We conclude that the hyponatremia may be caused by high secretion of prostagrandin and bradykinin associated with captopril therapy.
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PMID:[Severe hyponatremia associated with captopril therapy in dilated cardiomyopathy: a case report]. 268 97

The effects of the digitalis glycosides on systemic vascular resistance (SVR) in patients with congestive heart failure (CHF) are controversial. Most investigators report a reduction in total SVR, an action that has been attributed primarily to withdrawal of elevated sympathetic tone. Direct proof of this hypothesis is lacking, however, and the roles played by the renin-angiotensin-aldosterone and vasopressin systems have not been fully explored. Moreover, in several studies of patients with CHF, SVR did not decrease after the administration of digitalis. To clarify these issues, the hemodynamic and hormonal effects of digoxin were correlated in 11 normotensive men in sinus rhythm with CHF due to dilated cardiomyopathy. Patients were evaluated at rest and during submaximal exercise before and 6 hours after the intravenous infusion of 1.0 mg of digoxin (mean serum concentration 1.7 ng/ml). With digoxin therapy, heart rate, pulmonary wedge pressure and right atrial pressure declined and cardiac output increased. Although vasopressin was unchanged, both plasma norepinephrine concentrations and plasma renin activity decreased, the reduction in norepinephrine correlating with the increase in cardiac output. Despite these hemodynamic and hormonal effects, there was no change in total SVR at rest or during exercise. It is concluded that the improvement in cardiac function with digoxin in this patient group was a result of the inotropic properties of the drug, without an associated reduction in impedance. The failure of total SVR to decrease despite decreases in plasma norepinephrine levels and plasma renin activity might be explained by concomitant digitalis-induced vasoconstriction, impaired ability of arterioles to dilate in CHF, or offsetting alterations in other vasoactive hormone systems.
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PMID:Acute effects of digoxin on total systemic vascular resistance in congestive heart failure due to dilated cardiomyopathy: a hemodynamic-hormonal study. 390 88

In every patient with congestive heart failure there is a secondary neurohumoral response including increase in serum noradrenaline, renin, angiotensin, aldosteron and antidiuretic hormone or arginine-vasopressin values. Plasma and urine noradrenaline levels are increased proportionally to the severity of ventricular dysfunction, but its reserve is often reduced in the myocardium as well as the density of beta receptors and sensitivity to catecholamines and inotropic responses to the stimulation of adrenergic nerves. Down-regulation of beta-adrenoceptors in the myocardium, verified by the technique of radioligands, with the reduced number of beta-adrenoceptors, is accompanied by the appearance of refractoriness and desensitization to endogenous and exogenous catecholamines. Chronic beta-blockade may improve haemodynamic and clinical function in patients with dilated cardiomyopathy or congestive heart failure, because beta-blockers have potentially beneficial actions: protection of the myocardium from damage by chronic excessive catecholamine stimulation, restoration toward normal of the down-regulated membrane beta-receptor density often seen in heart failure, reduction in the risk of potentially lethal ventricular arrhythmias and beneficial effects on substrate utilization. Our results of investigation in 20 patients with congestive heart failure treated with beta-blockers short and long-term (average 22 months) gave substantial increases in ejection cardiac index and improved functional class and also improved working capacity.
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PMID:[Beta-adrenergic blockers in congestive heart failure: pro et contra?]. 1819 10

The pharmacological treatment of dilated cardiomyopathy overlaps with the treatment of heart failure. The primary objective of this treatment is to slow the progression of disease and improve quality and length of life. All patients, including those with asymptomatic dysfunction of the left ventricle, ought to receive angiotensin converting enzyme inhibitors, (in the case of intolerance, angiotensin receptor blockers), and beta blockers. The results of studies involving aliskiren have been, so far, disappointing. In symptomatic heart failure NYHA II-IV diuretics and mineralcorticoid receptor antagonists should be added to treatment. Digoxin is recommended in the event of atrial fibrillation, and otherwise only in the event of NYHA III and IV. Ivabradine is recommended for patients with sinus rhythm and pulse rate of > 70/min. In decompensation of heart failure, dobutamine, phosphodiesterase inhibitors or levosimendan are administered over the short-term. Of the recent treatment options, the vasopressin blocker and adenosine A1 receptor antagonist (rolofylline) were disappointing. One treatment with potential for the future is omecamtiv mecarbil, a heart myosin activator.
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PMID:Pharmacotherapy of dilated cardiomyopathy. 2548 45

A 43-year-old man was referred to our hospital in June 2014 because of severe heart failure. He was diagnosed with familial dilated cardiomyopathy and was administered oral tolvaptan and amiodarone for atrial and ventricular tachycardia. Since up-titration of carvedilol had failed and he was dependent on dobutamine, a left ventricular assist device (LVAD) was implanted. Tolvaptan and furosemide were both discontinued after LVAD implantation and he was discharged from the hospital. Thirteen months later, he was hospitalized for lethargy and hyponatremia of 108 mEq/L, with an antidiuretic hormone level of 2.5 pg/mL, which suggested syndrome of inappropriate antidiuretic hormone secretion (SIADH). We discontinued amiodarone and administered fludrocortisones. However, hyponatremia persisted for a few more days, eventually resulting in delirium and damage to the LVAD driveline. He received an urgent pump exchange and hyponatremia was gradually improved. We considered the possibility that amiodarone-induced SIADH was masked by tolvaptan therapy before LVAD implantation.
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PMID:Amiodarone-Induced Hyponatremia Masked by Tolvaptan in a Patient with an Implantable Left Ventricular Assist Device. 2915 94


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