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)

Atrial natriuretic factor (ANF) is a peptide hormone secreted by the heart that is degraded in vivo by endopeptidase 24:11 (atriopeptidase). UK 69,578 is a novel atriopeptidase inhibitor that raises plasma levels of ANF in animals and normal volunteers, with associated diuresis and natriuresis. This study examines the effects of UK 69,578 in patients with mild heart failure. UK 69,578 was administered as an intravenous infusion over 20 min in a placebo-controlled, cross-over study to six patients with stable (NYHA Class 2) chronic heart failure. The atriopeptidase inhibitor was well tolerated and no side effects were encountered. Mean baseline plasma ANF was elevated at 88 pg/mL (normal less than 50), and increased 2- to 5-fold after UK 69,578 administration. Plasma ANF did not change significantly following placebo. There was a marked diuresis after UK 69,578 compared to placebo. Urinary sodium excretion doubled for 4 to 6 h, but there was no significant rise in potassium excretion. There was no increase in plasma active renin concentration during the study period. Noninvasive hemodynamic monitoring revealed no significant changes in heart rate, systemic arterial blood pressure, or echocardiographic left ventricular dimensions. However, invasive measurements using a Swan-Ganz catheter demonstrated falls in mean right atrial and pulmonary artery wedge pressures after UK 69,578. There was no change in cardiac output. Thus, inhibition of endopeptidase 24:11 by UK 69,578 results in significant elevation of plasma ANF, with associated diuresis, natriuresis and venodilatation. The compound was well tolerated in these patients with mild chronic heart failure.
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PMID:Inhibition of the metabolism of atrial natriuretic factor causes diuresis and natriuresis in chronic heart failure. 214 74

In response to a meat meal containing 125 mEq of sodium, conscious dogs (n = 5) with an arteriovenous (AV) fistula and chronic compensated heart failure exhibited temporally related increases in postprandial plasma immunoreactive atrial natriuretic factor (iANF), right atrial pressure, and sodium excretion. In separate experiments, two weeks of dietary sodium restriction produced similar marked stimulation of renin and aldosterone both in normal dogs (n = 5), and in AV fistula dogs (n = 5) with chronic high circulating levels of ANF. Plasma iANF did not change (P greater than .05) in either group. These results suggest that the ANF system is involved in the postprandial regulation of sodium excretion in the AV fistula dogs with compensated heart failure. In the postabsorptive state, however, the activity of the renin-aldosterone axis is closely related to dietary sodium intake and appears to function independently of the ANF system for the prevention of sodium loss.
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PMID:The atrial natriuretic factor hormonal system in the regulation of sodium excretion in dogs with experimental heart failure. 214 76

Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p = 0.0001), plasma atrial natriuretic factor (p less than 0.0001), plasma arginine vasopressin (p = 0.006), and plasma renin activity (p = 0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased (p less than 0.05) in patients on diuretic therapy. We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure. Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy.
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PMID:Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). 214 40

Atrial natriuretic factor (ANF) is a cardiac hormone exerting potent cardiovascular and renal effects but its poor intestinal absorption and rapid inactivation have prevented so far its therapeutic utilisation. However inhibition of endogenous ANF metabolism progressively emerges as a novel therapeutic approach in cardiovascular and renal disorders. The critical role played by enkephalinase (membrane metalloendopeptidase, EC 3.4.24.11) in ANF inactivation was deduced from the effects of inhibitors. These compounds not only protect partially exogenous ANF from hydrolysis by some tissue preparations in vitro but also, in vivo, they increase the half-life of the exogenous hormone in plasma and, even more markedly, its recovery in intact form in kidney, a major target organ. In addition, enkephalinase inhibitors increase by two- to three-fold the circulating level of endogenous ANF, even when the latter is already markedly elevated, such as in patients with chronic heart failure. Finally, enkephalinase inhibitors induce a series of ANF-like responses such as natriuresis, diuresis or increase in cGMP excretion which are attributable to the hormone. These pharmacological observations, as well as preliminary clinical trials, suggest that enkephalinase inhibitors may represent a novel class of therapeutic agents with potential applications in congestive heart failure, essential hypertension and various sodium-retaining states.
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PMID:Enkephalinase (EC 3.4.24.11) inhibitors: protection of endogenous ANF against inactivation and potential therapeutic applications. 214 57

We investigated whether rats with high-output heart failure [aortocaval (AC) shunts] release atrial natriuretic factor (ANF) and excrete sodium after moderate volume expansion (VE) as do sham-operated controls. Mean arterial blood pressure was lower (92.5 +/- 4.4 vs. 114.0 +/- 1.3 mmHg) and relative heart weight was higher (545.6 +/- 35.1 vs. 253.8 +/- 9.8 mg/100 g body wt) in animals with AC shunts than in their controls. Central venous pressure (CVP) was elevated (3.61 +/- 0.36 vs. 0.37 +/- 0.94 mmHg) and heart rate decreased (332.5 +/- 8 vs. 370.0 +/- 9.9 beats/min) in AC rats. This group also presented lower basal urinary sodium excretion (UNaV), urinary volume, and hematocrit than their sham-operated controls. Basal plasma COOH- and NH2-terminal ANF levels were greatly elevated in AC shunt animals (165.43 +/- 55.73 and 1,692.98 +/- 305.63 fmol/ml, respectively) when compared with the controls (14.27 +/- 1.49 and 331.67 +/- 29.84 fmol/ml, respectively). VE was performed in conscious rats 3 times at 15-min intervals with human plasma protein fraction. The effect of VE on CVP, left-ventricular end-diastolic pressure, the increases in plasma COOH- and NH2-terminal ANF, and the diuretic and natriuretic responses were similar in both experimental groups. U(NA)V was positively correlated with plasma COOH- (r = 0.50, P less than 0.01) and NH2- (r = 0.60, P less than 0.001) terminal ANF only in the controls. One main peak of immunoreactive ANF corresponding to the elution time of a small peptide such as ANF-(99-126) was detected in the plasma of AC animals after VE. We conclude that ANF release and natriuresis are conserved after moderate VE in a rat model of moderate high-output experimental heart failure.
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PMID:Atrial natriuretic factor release and natriuresis in rats with high-output heart failure. 214 89

The failing heart is unable to provide some organs, notably the brain and the myocardium, with the amount of blood flow they require. To this myocardial inadequacy and resulting "circulatory insufficient" the body reacts by setting in action compensatory mechanisms which are "intracardiac" first (Starling's heterometric regulation, ventricular hypertrophy), then neurohormonal, with the activation of vasoconstrictor systems (noradrenergic system, renin-angiotensin-aldosterone system, arginine-vasopressin system) counterbalanced by the activation of vasodilator systems (vasodilator prostaglandins, atrial natriuretic factor and kinins). However, the vasoconstrictor systems outweigh the vasodilator systems. They create an excessive arterial and venous vasoconstriction, together with water-and-salt retention, which leads to an increase of left ventricular work during both systole and diastole and to a gradual worsening of the heart failure. The present-day treatment of heart failure aims at reducing the water-and-salt retention and at restoring the balance between the vasoconstrictor and vasodilator systems.
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PMID:[General physiopathology of chronic left ventricular insufficiency]. 214 35

A 43-year-old patient with mild heart failure attempted suicide by ingesting between 5000 and 7500 mg of captopril. Blood pressure oscillated around 100-120/50-75 mmHg and pulse rate showed no tendency to accelerate (75-100/min). The psychiatric examination showed no drug induced psychopathological symptoms. The calculated half-life of captopril was 4.4 h. Seven hours after ingestion of approximately 50 times the maximal therapeutic daily dose of captopril the serum concentration reached 20 micrograms/ml. The calculated amount of absorbed captopril was approximately 5400 mg. Atrial natriuretic factor (ANF) plasma levels were slightly elevated and showed no tendency to increase or to fall.
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PMID:Uneventful self poisoning with a very high dose of captopril. 214 47

The response in terms of production of atrial natriuretic factor to maximal cardiopulmonary exercise was investigated in 13 patients with mild heart failure (New York Heart Association function class II) secondary to previous myocardial infarction. Exercise induced a rapid and gradually increasing production of atrial natriuretic factor. The concentration at the termination of the test was statistically higher than at rest (64.5 +/- 9.7 versus 119.4 +/- 18.3 pmol/l. P = 0.001). Resting levels of the natriuretic factor correlated well to levels at peak exercise (r = 0.797, P = 0.001). The increase in concentration from rest to peak exercise (atrial natriuretic factor delta) was inversely correlated to the peak consumption of oxygen (r = -0.584, P = 0.036), indicating that the response to exercise is not attenuated in the patients with most marked functional impairment. The relationship between resting levels of atrial natriuretic factor and peak consumption of oxygen did not reach statistical significance (r = -0.421, P = 0.152), but a significant inverse relationship was observed between concentration at peak exercise and peak consumption of oxygen (r = -0.671, P = 0.012). Levels of atrial natriuretic factor during peak exercise are related to functional impairment in mild heart failure and may discriminate between the functional capacity of patients belonging in the same class of clinical function.
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PMID:Plasma atrial natriuretic factor concentration during maximal cardiopulmonary exercise in men with mild heart failure. 214 58

The effect of a single oral dose (50 mg) of captopril was studied in 12 hypertensive patients divided into 2 groups: 6 had a normal hemodynamic profile; the other 6 had NYHA class III or IV heart failure. Medical history and clinical and laboratory investigation showed that the heart failure was due exclusively to arterial hypertension. Mean arterial pressure (MAP), aldosterone, plasma renin activity (PRA) and atrial natriuretic factor (ANF) were followed for 4 hours after administration of captopril. MAP values showed a similar decrease in the 2 groups but the variations in the 3 hormones were much greater in the second group. This group showed higher basal levels of PRA, aldosterone and ANF; after stimulation PRA increased sharply preceded by a substantial decrease in aldosterone and ANF. To explain this phenomenon, the Authors propose that the liver of the patients with heart failure is unable to rapidly compensate the reduction in synthesis of angiotensin II caused by the drug with a corresponding increase in angiotensinogen production; the consequent sharp drop in plasma aldosterone would lead to a rise in renin production by the kidney. The arteriolar and venous vasodilatation induced by the ACE-inhibitor, would explain the drop in intra-atrial pressure with reduced plasma levels of ANF. The decrease in ANF could also be caused by the inhibition of the renin-angiotensin system of the heart leading to improved blood supply and hence myocardial contractility.
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PMID:[Captopril and hypertensive cardiopathy : therapeutic effects and hormonal changes]. 215 Mar 43

Transgenic mice expressing atrial natriuretic factor-SV40 T-antigen fusion genes (ANF-TAG) developed cardiac tumors asymmetrically in the right atrium. Features associated with cardiac failure, including increased plasma creatine kinase activity (MM and MB) and ventricular dysrhythmias, also were associated with atrial tumor growth. These atrial tumors were able to grow at histocompatible sites (subcutaneously in syngeneic animals) for protracted periods of time yielding a series of transplantable atrial tumor lineages. The transplantable tumors displayed several cardiac-specific characteristics, such as endogenous electrical activity and expression of cardiac-specific proteins. These transplantable atrial tumors constitute a novel experimental resource for developing cell lines which display an adult cardiac phenotype.
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PMID:Cardiac tumors and dysrhythmias in transgenic mice. 215 Oct 59


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