Skip Navigation

European Journal of Heart Failure 2006 8(6):628-633; doi:10.1016/j.ejheart.2005.11.018
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (5)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Larsen, A.I.
Right arrow Articles by Hall, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Larsen, A.I.
Right arrow Articles by Hall, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2005 European Society of Cardiology

The effect of altering haemodynamics on the plasma concentrations of natriuretic peptides in heart failure

A.I. Larsena,*, K. Dicksteina, N.S. Ahmadib, T. Aarslandc, J.T. Kvaløyd and C. Hallb

a University of Bergen, Cardiology Division, Stavanger University Hospital N-4001 Stavanger, Norway
b Akershus University Hospital, University of Oslo Norway
c Hjertelaget Research Foundation Rogaland, Norway
d Department of Mathematics and Natural Science, University of Stavanger, Division of Research and Human Resources, Stavanger University Hospital Norway

* Corresponding author. Tel.: +47 51518000; fax: +47 51519905. E-mail address: alfil{at}broadpark.nolaai{at}sir.no (A.I. Larsen).


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Limitations
 6. Conclusion
 Acknowledgment
 References
 
Background: Natriuretic peptide levels reflect haemodynamics in patients with heart failure and may serve as biochemical markers of cardiac filling pressures. The purpose of this study was to detect differences in the kinetic profile between atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their N-terminal fragments N-ANP and N-BNP, in response to rapid and persistent vasodilatation.

Methods: Sixteen men and four women aged 63.0 ± 10.4 (mean ± S.D.) with symptomatic congestive heart failure (NYHA III) and pulmonary capillary wedge pressure (PCWP) > 18 mm Hg, received a 24-h infusion of nitroglycerin (N = 8) or nicorandil (N = 12). A reduction of PCWP was achieved for the duration of the study. Natriuretic peptides were measured by radioimmunoassay at baseline, 1, 3, 6, 12 and 24 h.

Results: PCWP and right atrial pressure fell rapidly and then increased modestly. ANP and N-ANP demonstrated a similar pattern. In contrast, BNP and N-BNP levels fell steadily throughout the observation period. This was accompanied by a continuous reduction of systemic vascular resistance (SVR). PCWP was highly correlated to the levels of all the natriuretic peptides. Using a longitudinal regression model evaluating responses over time, we found separate, significant relationships between all peptides and haemodynamic variables

Conclusion: The atrial natriuretic peptides reflect rapid changes in filling pressures while the B-type peptides respond much slower. B-type peptides are less sensitive to short-term changes in filling pressures, but should reflect changes in SVR better during vasodilator therapy.

Key Words: Haemodynamics • Natriuretic peptides • Heart failure

Received April 30, 2005; Revised August 18, 2005; Accepted November 22, 2005


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 5. Limitations
 6. Conclusion
 Acknowledgment
 References
 
In patients with heart failure, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are found in increasing concentrations proportional to the severity of functional impairment [1,2], and the serum concentrations of both peptides are related to prognosis [3,4]. The natriuretic peptides partially counteract the vasoconstrictor hormones in that they have natriuretic, diuretic and vasodilatory properties [5].

N-terminal pro-ANP (N-ANP) and N-terminal pro-BNP (N-BNP) possess enhanced in vivo stability and higher plasma concentrations compared to that of the C-terminal biologically active fragments. Due to their longer half-life, they may reflect atrial pressures more accurately [6]. The in vitro stability of the N-terminal fragments also simplifies handling of samples [7,8].

Vasodilators reduce filling pressures in patients with congestive heart failure. Intravenous infusion of nitroglycerin is associated with a prompt reduction in PCWP [9], but patients frequently demonstrate haemodynamic tolerance to the drug [10]. Nicorandil, a nicotinamide ester, has nitrate-like properties, but the haemodynamic tolerance is limited, possible due its potassium channel opening properties [11]. The reduction of natriuretic peptide plasma concentration after intravenous infusion of vasodilators has been documented [12], but there is no comparative study on the response of the natriuretic peptides and their N-terminal fragments to rapidly changing haemodynamics in heart failure patients receiving intravenous vasodilator therapy. The purpose of the present study was to evaluate the kinetic behaviour of the peptides in response to an acute reduction in filling pressures during 24 h of continuous intravenous vasodilator therapy.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 5. Limitations
 6. Conclusion
 Acknowledgment
 References
 
This study was a double blind, randomised crossover trial evaluating the difference in development of tachyphylaxis between nitroglycerin and nicorandil during a 24-h intravenous infusion assessed by changes in pulmonary capillary wedge pressure (PCWP). The results with regard to tachyphylaxis are previously reported [11]. This sub-study is a post hoc analysis of the kinetic behaviour of the peptides in response to an acute reduction in filling pressures during 24 h of intravenous vasodilator therapy. Only data from the first randomisation was used in this sub-study.

2.1. Subjects
Twenty patients with stable heart failure in New York Heart Association (NYHA) class III (16 men and 4 women aged 63.0±10.4 years) were studied (Table 1). The subjects were on stable medical therapy receiving digitalis, diuretics, and angiotensin-converting enzyme (ACE) inhibitors for at least 14 days before inclusion. The aetiology of heart failure was coronary artery disease or idiopathic dilated cardiomyopathy. In all patients, the initial pulmonary capillary wedge pressure (PCWP) was ≥18 mm Hg and left ventricular ejection fraction (EF) was <40%. The study was approved by the Regional Ethics Committee and written informed consent was obtained from all patients.


View this table:
[in this window]
[in a new window]

  		Table 1 Patient characteristics (n=20)

 
2.2. Study design
On study day 1, each patient was randomly assigned to a treatment group. Nitroglycerin was administered to eight patients. The concentration of the nitroglycerin infusion was 0.4 mg/ml, and the maximal infusion speed was limited to 16 mg/h. The 12 remaining patients received nicorandil. The corresponding concentration of nicorandil was 0.576 mg/ml, and the maximal infusion speed was limited to 23 mg/h. This procedure allowed similar maximal infusion speeds for both drug regimens.

The study protocol is previously described. Briefly, a triple lumen pulmonary balloon catheter and a radial artery cannula was inserted on the evening prior to the study. All vasoactive medication was withheld. Baseline haemodynamic assessment was performed at 8:00 am, the inclusion criteria were verified and titration of vasodilator started. The infusion speed was titrated to obtain at least a 30% reduction in PCWP during a period of 3 h. The infusion rate was then maintained constant for 24 h. If a 30% decrease of PCWP was not achieved, a dose of 40 ml/h was infused for the remainder of the study period. Haemodynamic parameters were recorded at baseline and hours 1 through 3, 6, 8, 10, 12, and 22 through 24.

Blood samples were drawn for the measurement of the four cardiac peptides before the start of the infusion and then after 1, 3, 6, 12, and 24 h. The blood samples were drawn from the radial artery cannula into pre-chilled vacutainers and immediately centrifuged at 3000 rpm. Thereafter the plasma was frozen at –70 °C until assay.

2.3. Radioimmunoassay
The plasma BNP concentration was measured by an IRMA-kit for human BNP (Shionoria BNP, Shionogi & Co., Ltd.). The detection limit was 1.2 pmol/l and the between and within assay coefficients of variation were 9.3% and 3.3%, respectively. Recovery was 107% (n=7). The plasma N-BNP concentration was measured directly in plasma using a radioimmunoassay developed in-house with polyclonal antiserum raised in a rabbit immunized with N-BNP (Peninsula Laboratories Inc., CA) as antigen according to Schulz et al. [13]. The detection limit was 9.7 pmol/l and the between and within assay coefficients of variation were 9.0% and 7.3%, respectively. Recovery was 82% (n=10). The plasma ANP (irANP 99-126) concentration was measured in plasma using an IRMA-kit for a-human ANP (Shionoria ANP, Shionogi & Co., Ltd.). The detection limit for ANP was 1.40 pmol/l and the between and within assay coefficients of variation were 6% and 4.8%, respectively. Recovery was 75.4% (n=9). The plasma N-ANP (irANP 1-98) concentration was measured in unextracted plasma according to Sundsfjord et al. [14]. The detection limit for N-ANP was 185 pmol/l and the between and within assay coefficients of variation were 4.1% and 6.3%, respectively. Recovery was 85% (n=10).

2.4. Statistical analysis
The changes in haemodynamic parameters and natriuretic peptide plasma levels during the intravenous infusions were examined using SPSS 9.0 and R 1.9.1. Differences in paired data were evaluated using the two-tailed Student's t-test. Differences between groups were examined with a two-tailed t-test for unpaired data. The relationships between haemodynamic data and differences over time were analysed by Pearson's correlation coefficients. The data are reported as mean±1S.D. with p<0.05 regarded as significant. To evaluate the relationship between the relative values (percent reduction) of natriuretic peptides and haemodynamic variables in each individual, we used a longitudinal regression model [15]. This model describes the relationship between haemodynamic data and natriuretic peptides for patients during the 24-h observation period by a linear regression model taking into account the correlations within patients. Tests for relationship were done by testing whether the slopes of these regression lines differed significantly from zero.


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 5. Limitations
 6. Conclusion
 Acknowledgment
 References
 
Twenty patients completed the study per protocol.

3.1. Haemodynamic parameters
The primary efficacy parameter, PCWP, was reduced to 61±9% of the baseline value after 3 h and remained practically unchanged through 6 and 12 h, with a moderate increase after 24 h (Fig. 1, Table 2). The mean right atrial pressure (RAP) was reduced to 80±20% after 3 h. Maximal reduction of RAP was reached after 6 h, 74±15% of baseline. The 24-h reduction was to 84±25%. Cardiac output increased and the mean systemic vascular resistance showed a clear reduction at the end of the 24-h drug infusion. There was a borderline significant difference between the two types of nitrates with regard to percentage reduction in PCWP at 24 h (p=0.046) and a statistically significant difference with regard to the percentage reduction in SVR at 12 h (p=0.05). There were no other statistically significant differences in haemodynamic response between the two types of nitrate.


Figure 1
View larger version (20K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 (a-c) Levels of natriuretic peptides and some haemodynamic variables during 24 h of vasodilator nitrate therapy. ANP: atrial natriuretic peptide, BNP: brain natriuretic peptide, MRAP: mean right atrial pressure, PCWP: pulmonary capillary wedge pressure, N-ANP: N-terminal proatrial natriuretic peptide, N-BNP: N-terminal probrain natriuretic peptide, SVR: systemic vascular resistance.

 


View this table:
[in this window]
[in a new window]

  		Table 2 Haemodynamic measurements before and during administration of nitrates

 
3.2. Natriuretic peptide analysis
The kinetic profiles of the natriuretic peptides are reported in Table 3, and illustrated in Fig. 1. ANP and N-ANP fell rapidly within 3 h, and then tended to increase. In contrast, serum levels of both N-BNP and BNP decreased steadily throughout the observation period, reaching minimum levels at 24 h. There was a significant difference between the treatment groups only with regard to percentage reduction in serum levels of ANP at 3 h and N-ANP at 12 h, otherwise the peptide responses were independent of the type of nitrate administered.


View this table:
[in this window]
[in a new window]

  		Table 3 Natriuretic peptides before and during administration of nitrates

 
3.3. Relationship between plasma natriuretic peptide levels and haemodynamic parameters
Both the plasma-levels of N-BNP and BNP and SVR reached their lowest values at 24 h, but there was no significant correlation between the reduction in B-type natriuretic peptides and the reduction in SVR looking at each specific time point for the whole study group. A linear relationship between PCWP and plasma peptide levels was noted at baseline, and this was persistent at 3 h (Table 4). The correlation with PCWP after 24 h was significant only for the N-terminal types of both peptides.


View this table:
[in this window]
[in a new window]

  		Table 4 Pearson's correlation coefficients between simultaneous measurements of the four natriuretic peptides, PCWP, RAP and SVR at baseline and after 3 and 24 h of nitrate infusion

 
Using the longitudinal regression model evaluating the responses over time, we found separate significant relationships between all peptides and the haemodynamic variables PCWP, RAP and SVR. P-values are reported in Table 5.


View this table:
[in this window]
[in a new window]

  		Table 5 Relationship between peptides and haemodynamic variables using the longitudinal regression model evaluating the responses over time

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
5. Limitations
 6. Conclusion
 Acknowledgment
 References
 
This study reports precise information about natriuretic peptides and haemodynamic variables at specific points of time during continuous 24-h vasodilator treatment. The first novel finding was that there is a difference in time course between the atrial and B-natriuretic peptides during the study period of 24 h. Secondly, we found that the reduction in PCWP in each different patient was highly correlated to the relative decrease in both fragments of the natriuretic peptides. In addition, there were separate significant relationships between all peptides and haemodynamic variables when we employed a longitudinal regression model evaluating the responses over time.

4.1. Time course of natriuretic peptides
The finding of a minimum value for ANP after only 3 h of vasodilator therapy supports previous research on sublingual nitroglycerin-induced reductions in right atrial, pulmonary arterial, and pulmonary capillary wedge pressures which were associated with a simultaneous decrease in plasma ANP concentrations within minutes, indicating that ANP is released by a pressure-sensitive mechanism both in the atria and the ventricles [16,17].

The sensitivity of the atrial stretch response to changes in atrial filling pressures appears to be maintained in severe congestive heart failure [18,19]. Since the content of natriuretic peptides in the atrium is much greater than that in the ventricles, even a slight increase in natriuretic peptides secreted from the atria would significantly affect plasma levels [20], and because ANP is the predominant hormone in the atria, its serum-concentration will therefore increase the most.

The levels of both BNP and N-BNP continued to decrease during the study. This is consistent with the results from a previous study in which BNP reached the lowest value at the end of study period [21]. However, the present study reports the difference in kinetic behaviour between the two peptides during intravenous vasodilator therapy alone with no additional supplemental diuretics. Additionally, in this study, the differences are also present between the two N-terminal peptides.

The marked difference in time course is compatible with the findings reported in a study of the ACE inhibitor alacepril, which showed a decrease of plasma ANP only 1 h after administration of the drug, whereas BNP decreased after 6 h [22]. The difference in storage mechanism may explain these findings. While the adjustment of ANP and N-ANP release from granules in the atrial myocardium is a rapid process, only small amounts of B-type peptide are pre-stored. Therefore, regulation at the level of gene activation is necessary for secretory adjustments of BNP. These changes in gene activation take place more rapidly for BNP than for ANP. Furthermore, it should be noted that the B type peptides may also reflect the degree of ventricular injury and damage due to cardiotoxicity of several other neurohormones (i.e. endothelin) while A type peptides are primarily secreted as a result of altered haemodynamic status [23].

The difference in time course may also be related to the clearance of the hormones. Natriuretic peptides are cleared from the circulation by binding to specific peptide receptors and by proteolysis by peptidases. However, BNP seems to be more resistant to this degradation than ANP [24]. Natriuretic peptides are also metabolised in the pulmonary circulation. This metabolic clearance in the pulmonary circulation is reported to be higher for ANP than for BNP. In addition, the amount of ANP cleared in the pulmonary circulation is dependent on the amount of both ANP and BNP secreted from the heart. This is in contrast to the clearance of BNP which is dependent on the amount of BNP secreted from the heart [25]. Therefore, additional different mechanisms for synthesis, secretion, or degradation for the two natriuretic peptides in response to haemodynamically similar signals may be present. Although renal excretion is regarded as the main clearance mechanism for natriuretic peptides, little is known about the importance of these mechanisms in relation to other possible pathways.

4.2. Relationship between natriuretic peptides and haemodynamics
At 24 h, the correlations between PCWP and the neurohormones were only significant for the N-terminal and not the C-terminal fragments of the peptides.

Using a longitudinal regression model evaluating the responses over time, we found significant relationships between all the haemodynamic variables and the 4 peptides. This finding reinforces the impression that the peptide responses are dependent on the acute alterations in central haemodynamics. However, there was a difference in time course between the two peptides. While the A-type peptide decrease levelled off towards the end of the infusion period, the B-type natriuretic peptides continued to decrease during the 24-h infusion, and this decrease paralleled the time course of the reduction of SVR. Indeed, in the longitudinal regression model the highest statistical significance between SVR and the natriuretic peptides was between SVR and BNP. This finding suggests that the measurement of B-type natriuretic peptides in addition to assessing changes in clinical status during a longer time span may provide valuable information about the effect of treatment on the peripheral circulation. In contrast, measurements of A-type natriuretic peptides provide short-time information about central haemodynamics.

The prognostic significance of both hormones has been documented in several studies and the changes in the levels of natriuretic peptides may serve as a marker of the changes of clinical status. However, the present study demonstrates that there is a difference in response to the reduction of filling pressures with regard to the time course. This may suggest a different use of the two peptides in the clinical setting. While acute improvement in haemodynamic status is best assessed by measurements of ANP, the use of BNP reflects long-term changes. Since nitrates are routinely used in the acute treatment of myocardial infarction and congestive heart failure to rapidly reduce preload, ANP and N-ANP could be used to monitor their effect, while BNP might better reflect long-term haemodynamic changes.


   5. Limitations
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Limitations
6. Conclusion
 Acknowledgment
 References
 
This was a retrospective, post hoc analysis in a small population using 2 different types of vasodilators and we have no haemodynamic data beyond the 24-h measurements. Therefore, speculations about the behaviour of these peptides beyond this time point would be inappropriate. Due to these limitations, we are reluctant to draw any clinical implications. Further research to define the optimal use of these peptides clinically is needed. Although beta-blockers are part of conventional heart failure therapy, this was not the case at the time of data collection. Concurrent treatment with these drugs might have influenced the results in this study.


   6. Conclusion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Limitations
 6. Conclusion
Acknowledgment
 References
 
This study in patients with chronic CHF and NYHA class III symptoms demonstrates that an acute and sustained decrease in filling pressures induced by nitrate infusion is associated with a reduction in plasma levels of ANP, N-ANP, BNP and N-BNP. It also documents that the reduction in filling pressures is associated with different patterns in the reduction of A- and B-type peptides. In contrast to the early reduction of ANP and N-ANP, the B-type peptides decreased continuously during the 24-h drug infusion.


   Acknowledgment
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Limitations
 6. Conclusion
 Acknowledgment
References
 
We are grateful to Ellen Lund Sagen for expert technical assistance.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Limitations
 6. Conclusion
 Acknowledgment
 References
 

  1. Dickstein K., Larsen A.I., Bonarjee V., Thoresen M., Aarsland T., Hall C. Plasma proatrial natriuretic factor is predictive of clinical status in patients with congestive heart failure. Am J Cardiol (1995) 76:679–683.[CrossRef][Web of Science][Medline]
  2. Jourdain P., Funck F., Bellorini M., et al. Bedside B-type natriuretic peptide and functional capacity in chronic heart failure. Eur J Heart Fail (2003) 5:155–160.[Abstract/Free Full Text]
  3. Richards A.M., Nicholls M.G., Espiner E.A., et al. B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation (2003) 107:2786–2792.[Abstract/Free Full Text]
  4. Dickstein K., Aarsland T., Hall C. Plasma N-terminal atrial natriuretic factor: a predictor of survival in patients with congestive heart failure. J Card Fail (1997) 3:83–89.[CrossRef][Medline]
  5. Garcia R., Thibault G., Nutt R., Cantin M., Genest J. Comparative vasoactive effects of native and synthetic atrial natriuretic factor (NAF). Biochem Biophys Res Commun (1984) 119:685–699.[CrossRef][Web of Science][Medline]
  6. Mathisen P., Hall C., Simonsen S. Comparative study of atrial peptides ANP (1-98) and ANP (99-126) as diagnostic markers of atrial distension in patients with cardiac disease. Scand J Clin Lab Invest (1993) 53:41–49.[Web of Science][Medline]
  7. Downie P.F., Talwar S., Squire I.B., Davies J.E., Barnett D.B., Ng L.L. Assessment of the stability of N-terminal pro-brain natriuretic peptide in vitro: implications for assessment of left ventricular dysfunction. Clin Sci (Lond) (1999) 97:255–258.[Medline]
  8. Sundsfjord J.A., Thibault G., Larochelle P., Cantin M. Identification and plasma concentrations of the N-terminal fragment of atrial natriuretic factor in man. J Clin Endocrinol Metab (1988) 66:605–610.[Abstract/Free Full Text]
  9. Leier C.V., Bambach D., Thompson M.J., Cattaneo S.M., Goldberg R.J., Unverferth D.V. Central and regional hemodynamic effects of intravenous isosorbide dinitrate, nitroglycerin and nitroprusside in patients with congestive heart failure. Am J Cardiol (1981) 48:1115–1123.[CrossRef][Web of Science][Medline]
  10. Elkayam U., Kulick D., McIntosh N., Roth A., Hsueh W., Rahimtoola S.H. Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure. Circulation (1987) 76:577–584.[Abstract/Free Full Text]
  11. Larsen A.I., Goransson L., Aarsland T., Tamby J.F., Dickstein K. Comparison of the degree of hemodynamic tolerance during intravenous infusion of nitroglycerin versus nicorandil in patients with congestive heart failure. Am Heart J (1997) 134:435–441.[CrossRef][Web of Science][Medline]
  12. Kamijo T., Kamei K., Sugo I., Kamiyama T., Sudo H., Ohba Y.J. Hemodynamic and hormonal responses to nicorandil in a canine model of acute ischemic heart failure: a comparison with cromakalim and nitroglycerin. Cardiovasc Pharmacol (1999) 33:93–101.[CrossRef][Web of Science][Medline]
  13. Schulz H., Langvik T.A., Lund Sagen E., Smith J., Ahmadi N., Hall C. Radioimmunoassay for N-terminal probrain natriuretic peptide in human plasma. Scand J Clin Lab Invest (2001) 61. [33±42].
  14. Sundsfjord J.A., Thibault G., Larochelle P., Cantin M. Identification and plasma concentrations of the N-terminal fragment of proatrial natriuretic factor in man. J Clin Endocrinol Metab (1988) 66(3):605–610.[Abstract/Free Full Text]
  15. Diggle P.J., Heagerty P., Liang K.Y., Zeger S.L. Analysis of longitudinal data. (2002) Second edition. Oxford University Press.
  16. Keller N., Sykulski R., Thamsborg G., Storm T., Larsen J. Changes in atrial natriuretic factor during preload reduction with nitroglycerin in patients with congestive heart failure. Clin Physiol (1988) 8:57–64.[CrossRef][Web of Science][Medline]
  17. Yasue H., Yoshimura M., Sumida H., et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation (1994) 90:195–203.[Abstract/Free Full Text]
  18. Lewis B.S., Makhoul N., Dakak N., et al. Atrial natriuretic peptide in severe heart failure: response to controlled changes in atrial pressures during intravenous nitroglycerin. Am Heart J (1992) 124:1009–1016.[CrossRef][Web of Science][Medline]
  19. Webster M.W., Sharpe D.N., Coxon R., et al. Effect of reducing atrial pressure on atrial natriuretic factor and vasoactive hormones in congestive heart failure secondary to ischemic and nonischemic dilated cardiomyopathy. Am J Cardiol (1989) 63:217–221.[CrossRef][Web of Science][Medline]
  20. Ogawa Tsuneo, Linz Wolfgang, Stevenson Michelle, et al. Evidence for load-dependent and load-independent determinants of cardiac natriuretic peptide production. Circulation (1996) 93:2059–2067.[Abstract/Free Full Text]
  21. Johnson W., Omland T., Hall C., et al. Neurohormonal activation rapidly decreases after intravenous therapy with diuretics and vasodilators for class IV heart failure. J Am Coll Cardiol (2002) 39:1623–1629.[Abstract/Free Full Text]
  22. Yoshimura M., Yasue H., Tanaka H., et al. Responses of plasma concentrations of A type natriuretic peptide and B type natriuretic peptide to alacepril, an angiotensin-converting enzyme inhibitor, in patients with congestive heart failure. Br Heart J (1994) 72:528–533.[Abstract/Free Full Text]
  23. Maeda K., Tsutamoto T., Wada A., Hisanaga T., Kinoshita M. Plasma brain natriuretic peptide as a biochemical marker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction. Am Heart J (1998) 135:825–832.[CrossRef][Web of Science][Medline]
  24. Smith M.W., Espiner E.A., Yandle T.G., Charles C.J., Richards A.M. Delayed metabolism of human brain natriuretic peptide reflects resistance to neutral endopeptidase. J Endocrinol (2000) 167:239–246.[Abstract]
  25. Yoshimura M., Mizuno Y., Harada E., et al. Interaction on metabolic clearance between A-type and B-type natriuretic peptides in patients with heart failure. Metabolism (2000) 49:1228–1233.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (5)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Larsen, A.I.
Right arrow Articles by Hall, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Larsen, A.I.
Right arrow Articles by Hall, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?