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)

The neurohormonal vasoconstrictor systems are frequently activated in patients with congestive heart failure, and they make important contributions to characteristic abnormalities in vasoconstriction. In 177 patients with congestive heart failure, however, there was a widespread distribution of levels of plasma renin activity and plasma norepinephrine, indicating that activation of the renin-angiotensin system and the sympathetic nervous system was not uniform. Furthermore, there were only weak correlations between plasma renin activity and plasma norepinephrine and hemodynamic measurements, age, and renal function, indicating that activation of these systems is complex and determined by many other factors. The converting enzyme inhibitors have beneficial effects on the hemodynamic abnormalities of patients with heart failure, with reductions in arterial tone and preload as well as increases in cardiac output. Their long-term effects on markers of the renin-angiotensin system, however, and their interactions with the sympathetic nervous system and atrial natriuretic factor are less well defined.
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PMID:Neurohormonal activation and the response to converting enzyme inhibitors in congestive heart failure. 213 52

The atrial natriuretic factor (ANF) is a hormone whose effects and mode of secretion have been determined. But its exact role in the regulation of volemia in comparison with that of the renin-angiotensin system is still to be defined. Studies of human diseases associated with an increase of ANF plasma concentration may help reach this goal. The mechanisms resulting in elevated ANF plasma concentrations (increase of secretion, decrease of catabolism of the hormone) and the effects of these high levels of ANF on renal functions and circulation are analysed in chronic cardiac failure, mitral stenosis, pulmonary artery hypertension, acute tachycardias, chronic and acute renal failures and in the course of cardiac transplantation. The therapeutic usefulness of drugs inhibiting ANF catabolism (blockers of the clearance receptors for ANF and inhibitors of the enzymes degrading ANF) is also considered.
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PMID:[Atrial natriuretic factor. Role in the physiopathology of cardiac and renal diseases]. 213 35

The changes in plasma immunoreactive atrial natriuretic factor (iANF) and urinary Na excretion that occur in response to an oral load of Na and to infusion of synthetic atrial natriuretic factor (ANF) were examined in conscious dogs with an arteriovenous (AV) fistula and chronic compensated high-output heart failure. After ingestion of a meal containing 125 meq Na, plasma iANF and right atrial pressure increased from high basal levels of 506 +/- 46 pg/ml and 96 +/- 5 mmH2O to peak responses of 728 +/- 43 pg/ml (P less than 0.05) and 104 +/- 6 mmH2O (P less than 0.05). These increases were associated with a brisk postprandial natriuresis and diuresis of a magnitude previously observed in normal dogs. Synthetic ANF infusions that achieved plasma iANF levels of similar and higher magnitude to those observed during the feeding experiments did not produce a significant natriuresis in these AV fistula dogs. In separate series of experiments, chronic effects of normal and low-Na diets on daily Na excretion and postabsorptive plasma iANF, renin, and aldosterone were studied in normal and AV fistula dogs. During the normal Na diet of 40 meq/day, both groups had normal levels of renin and aldosterone, but Na balance was achieved in AV fistula animals in the presence of a fourfold elevation in plasma iANF compared with normal dogs (P less than 0.05). During 2 wk of Na restriction, cumulative negative Na balance and marked stimulation of renin and aldosterone were similar in normal and AV fistula animals, but plasma iANF did not change significantly in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ANF and postprandial control of sodium excretion in dogs with compensated heart failure. 213

Elucidation of the role of (elevated) endogenous atrial natriuretic factor (ANF) in chronic heart failure has been hampered by a lack of specific inhibitors. We used a newly developed monoclonal antibody that has been shown to specifically block both exogenously and endogenously released ANF in vivo. For assessment of the vasodilatory action of ANF in chronic heart failure, either this antibody against ANF or ascites (control serum) was injected in rats with myocardial infarction and failure and in sham animals. Ascites did not alter central hemodynamics in either the sham or infarcted group. Antibody significantly increased right atrial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance (SVR) in the infarction group but did not affect these variables in the sham group. Because renal blood flow, as measured by radioactive microspheres, decreased significantly in all four groups, probably due to nonspecific renal vasoconstrictor effects of the ascites, a separate group of infarcted animals was treated with purified ANF antibody (devoid of nonspecific effects) or mouse IgG as a control injection. In these animals, right atrial pressure increased from 1.1 +/- 0.7 to 2.6 +/- 0.7 mm Hg (p less than 0.001). Although SVR, renal blood flow velocity (measured by Doppler probe), and renal vascular resistance did not change in the infarcted animals after administration of purified ANF antibody, a significant correlation was found between baseline plasma ANF values and the change in SVR exerted by purified ANF antibody (r = 0.758, p less than 0.02, n = 9); that is, SVR increased in rats with high baseline plasma ANF (greater than 350 pg/ml), but decreased in animals with plasma ANF less than 200 pg/ml. These results suggest that moderately elevated endogenous plasma ANF levels in chronic heart failure do affect central hemodynamics, primarily by reducing venous pressure (e.g., by decreasing intravascular volume or by venous dilation). Arterial vasodilation, however, appears to emerge when plasma ANF is greatly increased.
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PMID:Vasodilatory action of endogenous atrial natriuretic factor in a rat model of chronic heart failure as determined by monoclonal ANF antibody. 213 23

Plasma atrial natriuretic factor, aldosterone, renin activity, and antidiuretic hormone were studied in low output heart failure syndromes: cardiogenic shock in ten patients with acute myocardial infarction of the anterior wall (first group), hypovolemic shock after melena from peptic ulcer in ten subjects (second group), and hypotension with bradycardia syndrome in ten patients with acute myocardial infarction of the inferior wall (third group). Circulating atrial natriuretic factor in patients with cardiogenic shock (102.4 +/- 7.4 pg/ml) was significantly higher than in healthy volunteers matched for sex and age (8.4 +/- 0.3 pg/ml). In these patients there was a positive correlation between atrial natriuretic factor and central venous pressure values. Atrial natriuretic factor and central venous pressure values in the second and third groups were within normal range. Plasma aldosterone was high in all groups, plasma renin activity was elevated in the first and third groups, and high antidiuretic hormone was observed in the first and second groups. These findings indicate that in low output heart failure syndromes only hemodynamic changes affecting the atria stimulate atrial natriuretic factor release. No correlations were found between plasma atrial natriuretic factor and other hormones. In particular, high atrial natriuretic factor levels in the patients with cardiogenic shock did not inhibit release of aldosterone, renin, or antidiuretic hormone. It may be surmised that in these patients the hemodynamic effects override the inhibitory effects of atrial natriuretic factor.
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PMID:Plasma atrial natriuretic factor in low output heart failure syndromes. 213 7

The hemodynamic, renal, neurohormonal effects and pharmacokinetics of synthetic atrial natriuretic factor (ANF) were studied in six conscious dogs with severe heart failure induced by right ventricular pacing at 250 beats/min for 5.0 +/- 0.6 weeks. Severe heart failure was characterized by a low cardiac output (2.1 +/- 0.1 L/min, elevated pulmonary capillary wedge pressure (26.8 +/- 2.8 mmHg) and right atrial pressure (14.5 +/- 2.2 mmHg). Synthetic ANF (human 99ser-126tyr ANF) was administered intravenously as 2 consecutive 30 min infusions (0.02 and 0.10 microgram/kg.min respectively); and each infusion was preceded by a priming dose of 1 microgram/kg. In contrast to the potent vasorelaxant, natriuretic and renin-lowering effects previously reported in normal dogs, these effects were not observed in the dogs with heart failure with either dose of ANF. The plasma half-life was 10.0 +/- 2.6 min, significantly longer than that reported previously in normal dogs. These data suggest that in this model of heart failure, the pharmacokinetics of ANF are altered and there is generalized target organ resistance to the actions of ANF.
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PMID:Pharmacokinetics, hemodynamic, renal, and neurohormonal effects of atrial natriuretic factor in experimental heart failure. 214 31

Increases in sodium delivery to the distal nephron reduce glomerular filtration rate (GFR) via tubuloglomerular feedback (TGF). Central volume expansion and pharmacological concentrations of atrial natriuretic factor (ANF) are known to attenuate this response. To test the hypothesis that whole kidney TGF is attenuated by pathophysiological concentrations of ANF, hypertonic saline was given intrarenally in five dogs receiving an intravenous infusion of synthetic ANF at 20 ng.kg-1.min-1. To examine whole kidney TGF responses in heart failure, six additional dogs with acute congestive heart failure induced by rapid ventricular pacing also received intrarenal hypertonic saline. Seven sham-paced dogs served as controls. An isolated increase in circulating ANF from 26 +/- 3 to 342 +/- 23 pg/ml abolished the whole kidney GFR response to hypertonic saline. In acute congestive heart failure, the GFR response to hypertonic saline was not attenuated despite acute central volume overload and similar increases in circulating ANF. This intact response to hypertonic saline in acute congestive heart failure may contribute to the renal sodium retention characteristic of congestive heart failure.
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PMID:Atrial natriuretic factor modulates whole kidney tubuloglomerular feedback. 214 63

The response of atrial natriuretic factor to an acute increase in atrial pressures produced by changing from a 45 degrees upright to a -15 degrees Trendelenburg tilt was examined in 21 patients with heart failure and 8 control subjects with normal hemodynamics. In the control subjects, baseline (45 degrees upright tilt) pulmonary capillary wedge and right atrial pressures increased from 3.1 +/- 0.9 (mean +/- SEM) and 4.4 +/- 0.3 mm Hg to 6.9 +/- 1.9 and 8.5 +/- 0.4 mm Hg, respectively (p less than 0.05 for both), 30 min after the -15 degrees tilt. Baseline arterial plasma atrial natriuretic factor concentration increased from 34 +/- 4 to 44 +/- 1 pg/ml (p less than 0.05) 30 min after the tilt, with an increase observed in every patient. In the group with heart failure, baseline pulmonary capillary wedge and right atrial pressures increased from 17.5 +/- 2.0 and 5.3 +/- 1.2 mm Hg to 24.6 +/- 1.8 and 9.7 +/- 1.3 mm Hg, respectively (p less than 0.01 for both), 30 min after the tilt. Plasma atrial natriuretic factor concentration was 326 +/- 38 pg/ml at baseline and 347 +/- 34 pg/ml (p = NS) 30 min after tilt. Compared with the 7 patients with heart failure who had increased atrial natriuretic factor concentrations after the tilt (responders), the 14 patients with unchanged or decreased atrial natriuretic factor concentrations after the tilt (nonresponders) had a higher baseline right atrial pressure and atrial natriuretic factor concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of atrial natriuretic factor to postural change in patients with heart failure versus subjects with normal hemodynamics. 214 66

The effects of an orally active inhibitor (UK 79300) of the neutral metalloendopeptidase EC 3.4.24.11 were investigated in six healthy male volunteers maintained on a constant diet (150 mmol sodium/day and 80 mmol potassium/day). Subjects were studied in a random order, single-blind study on two occasions, each 48 hours in length, when they were given UK 79300 (25 or 50 mg p.o.) or placebo at 12-hour intervals (each agent for 24 hours). The endopeptidase inhibitor enhanced plasma concentrations of atrial natriuretic factor in association with suppression of both plasma renin activity and aldosterone concentrations. Twenty-four-hour urinary excretion of sodium was doubled by UK 79300, and the urinary excretion rates of phosphorus, atrial natriuretic factor immunoreactivity, and cyclic guanosine monophosphate were also significantly enhanced, whereas urinary aldosterone excretion was halved. The profile of biological effects closely paralleled those previously reported with low dose infusions of atrial natriuretic factor in humans and animals. Therapeutic trials of such inhibitors are now indicated for hypertension or heart failure together with further studies to clarify the underlying mechanisms of action.
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PMID:Inhibition of endopeptidase EC 24.11 in humans. Renal and endocrine effects. 214 60

The endopeptidase EC 3.4.24.11 (atriopeptidase) degrades atrial natriuretic factor (ANF). Intravenous administration of UK 69,578 (0.025 to 10.0 mg/kg), a new specific atriopeptidase inhibitor, in 16 normal volunteers produced a two- to three-fold rise in endogenous ANF. Peak levels were reached within 2 h declining to control values by 8 h. The rise in ANF was associated with an increase in urine volume and mean urinary sodium excretion rose from 64.9 mmoles/8 h after placebo to 116.1 mmoles/8 h after 10 mg/kg UK 69,578. Despite the natriuresis, plasma active renin concentration was suppressed for up to 8 h. We conclude that inhibition of the endopeptidase EC 3.4.24.11 in humans elevates endogenous ANF and causes a natriuresis and may offer a novel therapeutic approach to the treatment of hypertension and cardiac failure.
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PMID:The atriopeptidase inhibitor UK 69,578 increases atrial natriuretic factor and causes a natriuresis in normal humans. 214 71


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