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)

1. The present studies examined the effect of (a) a specific endopeptidase-24.11 (E-24.11) inhibitor (candoxatrilat) and (b) a ligand for the atrial natriuretic peptide (ANP) clearance receptor (SC 46542) on the renal and blood pressure response to brain natriuretic peptide (BNP) in conscious rats. 2. Infusion of BNP 200 ng kg-1 min-1 for 60 min produced a small rise in urinary sodium and guanosine 3':5'-cyclic monophosphate (cyclic GMP) excretion with a non-significant fall in mean arterial blood pressure. 3. Candoxatrilat (3 mg kg-1) alone had no significant effect on sodium excretion or blood pressure but markedly potentiated the natriuretic response to BNP. 4. Similarly SC 46542 (68 micrograms kg-1; 6.8 micrograms kg-1 min-1) which produced no significant effect on its own, potentiated the natriuresis-induced by BNP, although the effect was of shorter duration compared to that of candoxatrilat. 5. The data indicate two approaches to the potentiation of the renal activity of BNP and suggest that BNP may mediate some of the activity of E-24.11 inhibitors reported in cardiac failure.
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PMID:Effect of endopeptidase-24.11 inhibition and of atrial natriuretic peptide clearance receptor ligand on the response to rat brain natriuretic peptide in the conscious rat. 822 Aug 96

The human heart secretes both atrial natriuretic peptide and brain natriuretic peptide. This study attempts to clarify the pathophysiological significance of the peptides in cardiovascular diseases. Using immunoradiometric assay, plasma brain natriuretic peptide and atrial natriuretic peptide levels in essential hypertension, various secondary hypertension, chronic renal failure, chronic heart failure during cardiac pacing, and acute myocardial infarction were determined. Mean plasma brain natriuretic peptide and atrial natriuretic peptide levels in healthy subjects were 3.7 +/- 0.3 and 5.7 +/- 0.3 pmol/L, respectively, and increased as a function of age. Plasma brain natriuretic peptide levels showed a larger increase than atrial natriuretic peptide levels in various cardiovascular diseases. In chronic renal failure, whereas plasma atrial natriuretic peptide levels decreased significantly after hemodialysis and were correlated with the changes in body weight, changes in plasma brain natriuretic peptide levels were less prominent and did not show such a correlation. In chronic heart failure, both basal plasma brain natriuretic peptide and atrial natriuretic peptide levels were also significantly elevated. However, in response to acute ventricular or atrial pacing, brain natriuretic peptide levels did not show any increase in contrast to the marked increase of atrial natriuretic peptide levels. In acute myocardial infarction, brain natriuretic peptide levels showed more prominent changes than atrial natriuretic peptide levels and were correlated with serum levels of creatine kinase and cardiac myosin light chain I in most patients. These results suggest that both brain and atrial natriuretic peptides play an important role in the regulation of cardiovascular homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial and brain natriuretic peptides in cardiovascular diseases. 828 65

Natriuretic peptides family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), while receptors for these natriuretic peptides comprise at least three subtypes, i.e. A-type (GC-A), B-type (GC-B) and C-type (clearance). ANP and BNP are cardiac hormones mainly synthesized and secreted by atria and ventricles, respectively, but CNP is a neuropeptide synthesized by brain. Both A- and B-type receptors contain particulate guanylate cyclase within their molecule and mediate biological function via cyclic GMP as a second messenger, whereas C-type receptor is involved in clearance and metabolism of natriuretic peptides. In heart failure, cardiac expression of both ANP and BNP is augmented with increased circulating levels as a cardiac compensatory mechanism. Pathophysiological significance of natriuretic peptides system in heart failure is discussed.
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PMID:[Natriuretic peptide family]. 839 34

A RIA for human brain natriuretic peptide (BNP) was developed. Both BNP and atrial natriuretic peptide (ANP) were extracted from human plasma with Vycor glass powder (71% recovery for BNP). The assay had a minimum detection limit of 0.45 fmol/tube and an IC50 of 9 fmol/tube. The within-assay coefficients of variation were 11.4% at 4 pmol/L and 3.2% at 22 pmol/L, and the between-assay coefficient of variation was 11% at 24 pmol/L. There was no significant loss of immunoreactive (IR)-BNP in plasma samples stored at -80 C for 4 weeks. Low rates of labeled BNP and IR-BNP degradation occurred in EDTA plasma incubated at 37 C. The mean venous plasma IR-BNP (6.3 +/- 0.3 pmol/L) in normal subjects (n = 48) was significantly lower than plasma ANP (8.4 +/- 0.6 pmol/L). In contrast to ANP, IR-BNP did not increase when normotensive or hypertensive subjects changed from erect to supine posture. Markedly elevated levels were found in patients with congestive heart failure (mean IR-BNP, 87 +/- 11 pmol/L; ANP, 87 +/- 12 pmol/L; n = 35), recent myocardial infarction (mean IR-BNP, 60 +/- 9 pmol/L; ANP, 33 +/- 6 pmol/L; n = 7), and chronic renal failure. High pressure liquid chromatography of plasma extracts from heart failure subjects revealed both high (mol wt, 10,000) and low (mol wt, 4,000) mol wt IR-BNP. High mol wt BNP was the major component (mean ratio, 1.9:1) and was linearly correlated with low mol wt BNP (r = 0.99). HPLC of plasma extracts from three normal subjects receiving constant infusions of human BNP (2 pmol/kg.min) showed a single major peak eluting in the position of hBNP-32, with no evidence of high mol wt material. These results show that whereas marked elevations in BNP occur in circulatory disorders, a major (> 50%) and consistent contribution to immunoreactivity is due to precursor forms. Further, compared to ANP, there is no IR-BNP response to supine posture in normal and hypertensive subjects.
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PMID:Assay of brain natriuretic peptide (BNP) in human plasma: evidence for high molecular weight BNP as a major plasma component in heart failure. 847 92

Atrial natriuretic factor (ANF) is a peptide hormone secreted by the atria in response to increased transmural pressure. This peptide is the first of a series of natriuretic hormones which also includes brain natriuretic peptide (BNP). It is destroyed mainly by an ubiquitous enzyme, neutral endopeptidase (NEP). Its main actions are vasodilatation and natriuresis. It is the main physiological agonist of the renin/angiotensin/aldosterone system. In elderly subjects free of cardiovascular disease, baseline concentrations are higher than in younger subjects. In patients with congestive heart disease (CHD), the level of ANF rises due to permanent increased filling pressures. Both atrial and ventricular secretion increase ANF levels which loose their day/night rhythm. ANF is a risk factor independent of mortality, rhythm disorders and acute heart failure in patients with heart failure. BNP is also raised in CHD. There is an inverse correlation between concentration and severity of left ventricule dysfunction. There has been little work on ANF in elderly subjects with CHD. ANF is elevated in these patients and is an independent risk factor for cardiac decompensation. In addition, in very elderly subjects where the diagnosis of CHD is difficult and echocardiography not always possible, assay of BNP could be an interesting diagnostic tool. Currently work on therapeutic possibilities (administration of exogenous ANF, combinations with NEP inhibitor/conversion enzyme inhibitor, ANF/diuretics) have revealed certain problems (short half life of ANF, transient effects, non-specific activity of NEP). The usefulness of ANF and BNP in heart failure in elderly subjects will undoubtedly lie in its capacity to mark disease severity and as a diagnostic tool, particularly in case of acute dyspnoea.
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PMID:[Atrial natriuretic factor and brain natriuretic peptide. Variations in elderly subjects with heart failure]. 854 37

We measured plasma concentrations of adrenomedullin (AM), a novel bioactive peptide with potent vasodilator activity, in 21 patients with chronic congestive heart failure due to various heart diseases and compared them to levels in age- and sex-matched healthy subjects to examine the pathophysiological role of plasma AM in heart failure. In addition, the relationship between plasma AM and other hormones known to control the cardiovascular system was examined in these patients. The plasma AM level in the patients with heart failure was significantly (P < 0.01) higher than that in the control subjects (mean +/- SEM, 2.94 +/- 0.15 fmol/mL; n = 16), with a significantly (P < 0.05) higher concentration in patients in class III or IV (11.82 +/- 1.81 fmol/mL; n = 5) of the New York Heart Association functional classification than in those in class I or II (8.74 +/- 0.44 fmol/mL; n = 16). There were no significant correlations between plasma AM and catecholamine levels, whereas the plasma AM level was significantly correlated with the concentrations of plasma atrial natriuretic peptide (r = 0.58; P < 0.01), brain natriuretic peptide (r = 0.47; P < 0.05), and PRA (r = 0.77; P < 0.01) in the patients. Thus, the plasma AM concentration increased in proportion to the severity of heart failure along with the hormones known to modulate the development of congestive heart failure. The present findings suggest a possible role for AM as a circulating hormone participating in the defense mechanism against further deterioration of congestive heart failure in patients with heart disease.
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PMID:Plasma adrenomedullin concentration in patients with heart failure. 855 Jul 49

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are both circulating plasma hormones that are secreted by the heart and have similar physiological effects. We have shown previously that abrupt increases in plasma BNP in normal humans impair the clearance of ANP from plasma and result in additive physiological effects. Because large increases in plasma ANP are reported to have no effect on plasma BNP levels in patients with heart failure, we have studied ANP-BNP interactions in eight normal male subjects receiving background infusions of BNP (2 pmol.kg-1.min-1 for 5 h). Each subject also received a coinfusion of ANP ("active" day, 2 pmol.kg-1.min-1 for 2 h) or vehicle ("placebo" day) using a balanced random order, single-blind design. Metabolic clearance rate of ANP (mean 4.1 +/- 0.6 l/min) and disappearance rate from the plasma (t1/2 3.4 +/- 0.3 min) were similar to values measured previously in the absence of exogenous BNP. In contrast, steady-state plasma BNP levels were reversibly increased (mean BNP increment 10 pmol/l) during the administration of ANP (P = 0.038). Associated with these changes were significant (additive) physiological effects. Thus the addition of ANP increased plasma and urine guanosine 3',5'-cyclic monophosphate (P < 0.001 for both) and lowered systolic blood pressure (P = 0.049). When ANP was coinfused, significant differences were also observed in urine volume (P = 0.001) and sodium excretion (P = 0.043) between the infusion period (when urine volume and sodium excretion were enhanced) and postinfusion period (when values decreased). Taken together, our findings of similar interactions between ANP-BNP and BNP-ANP infusions occurring at pathophysiological concentrations of these two peptides, suggest that the interactions result from dissociation of prebound hormone, presumably from biological or clearance receptors.
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PMID:Interactions of atrial and brain natriuretic peptides at pathophysiological levels in normal men. 859 42

Plasma concentrations of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated in severe hypertension, acute myocardial infarction, and heart failure. In the current study of individuals with essential hypertension, we have documented the hemodynamic, hormonal, and endocrine effects of infusions of these two peptides given alone or in combination in equimolar doses calculated to induce increments in plasma peptides to concentrations (30 to 60 pmol/L) observed in these disease states. The metabolic clearance rate of ANP (4.56 +/- 0.62 L/min) was greater than that for BNP (3.4 +/- 0.23 L/min, P <.001). Infusions of each cardiac hormone impaired the clearance of coinfused peptide. All peptide infusions enhanced natriuresis (17% to 70% above preinfusion levels versus placebo, 6%; P <.001), lowered blood pressure (10 to 18 mm Hg fall in mean arterial pressure below placebo levels; P <.001), increased hematocrit, suppressed the renin-angiotensin-aldosterone system, and enhanced plasma norepinephrine concentrations. The natriuretic and blood pressure-lowering effects of BNP were twofold to threefold those of ANP. In contrast, ANP-induced increments in plasma and urinary second messenger (cGMP) levels were greater than those for BNP. Both peptides suppressed the renin-angiotensin-aldosterone system (approximately one-third fall in renin activity and plasma aldosterone) and enhanced plasma norepinephrine concentrations (+30%) to a similar degree. Increments in plasma ANP and BNP that occur simultaneously in cardiovascular disease states appear capable of causing hemodynamic, endocrine, and renal effects that would tend to ameliorate conditions such as hypertension or heart failure.
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PMID:Differing metabolism and bioactivity of atrial and brain natriuretic peptides in essential hypertension. 861 67

We investigated the usefulness of the plasma concentration of brain natriuretic peptide (BNP) for evaluating cardiac function in patients with Duchenne muscular dystrophy (DMD). The plasma BNP concentration was measured by immunoradiometric assay in 55 patients with DMD and in 34 healthy subjects. Cardiac function was evaluated by the cardiothoracic ratio (CTR) on chest roentgenogram, left ventricular end-diastolic dimension (LVDd) and fractional shortening (FS) on echocardiogram, and the ratio of ejection time to pre-ejection period (ET/PEP) on mechanocardiogram. The function of skeletal muscle was evaluated in terms of the disability of lower limb function, serum creatine kinase (CK) activity and % vital capacity (% VC). The plasma concentration of BNP was increased in patients with DMD (32.7 +/- 14.8 pg/ml, mean +/- SEM) compared with that in normal subjects (4.3 +/- 0.5 pg/ml). Two of the DMD patients had symptoms of heart failure, with markedly increased plasma BNP concentrations. The other DMD patients with increased plasma BNP concentrations showed abnormal cardiac function but no symptoms of heart failure. In addition, in patients with DMD, the plasma BNP concentration showed significant positive correlations with CTR and LVDd (p < 0.01), and negative correlations with ET/PEP and FS (p < 0.01). In severe DMD patients who had advanced disability and decreased CK activity, the plasma BNP concentration tended to be elevated. There was no significant correlation between the plasma BNP concentration and % VC. These findings suggest that the plasma BNP concentration is useful for evaluating cardiac dysfunction, whether manifest or latent, in patients with DMD, in whom accurate evaluation of cardiac function by conventional methods is difficult due to severe muscle atrophy and deformity of the thorax.
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PMID:[Estimation of cardiac function by plasma concentration of brain natriuretic peptide in patients with Duchenne muscular dystrophy]. 868 97

Although elevations of plasma atrial natriuretic peptide (ANP) concentrations have been shown to have prognostic significance in patients after acute myocardial infarction (AMI), the relation between plasma levels of B-type natriuretic peptide (BNP) and cardiovascular mortality remains unknown. To test the prognostic value of plasma ANP and BNP after AMI, plasma concentrations were measured a mean of 3 days after infarction in 75 patients. During a median follow-up of 19.7 months, 14 patients (18.4%) died of cardiovascular causes. On univariate analysis, plasma ANP and BNP, Killip class, modified Peel index, left ventricular ejection fraction, and presence of left ventricular failure were all associated with cardiovascular mortality. In contrast, plasma ANP was the only variable that correlated with the development of symptomatic heart failure and hospitalization. For the combined end point of cardiovascular mortality, symptomatic heart failure, and hospitalization, plasma neurohormones were the only variables of predictive value. By stepwise regression analysis, plasma BNP was the only significant independent predictor of cardiovascular mortality (p = 0.001), whereas plasma ANP identified patients at risk of symptomatic heart failure and hospitalization (p = 0.002 and 0.019, respectively). This study indicates that plasma BNP measured after AMI is a powerful neurohormonal predictor of subsequent cardiovascular mortality, whereas plasma ANP correlates better with the development of symptomatic heart failure and hospitalization. Routine measurement of both of these peptides in the period immediately after an AMI may provide a simple means of risk stratification with different information gained from each peptide.
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PMID:Diagnostic value of B-type natriuretic peptide concentrations in patients with acute myocardial infarction. 875 5


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