(Circulation. 1996;93:1946-1950.)
© 1996 American Heart Association, Inc.
Articles |
New Insights Into the Cardiac Natriuretic Peptides
From the Division of Cardiology, Northwestern University Medical School, Chicago, Ill.
Correspondence to Robert O. Bonow, MD, Division of Cardiology, Northwestern University Medical School, 250 E Superior St, Suite 524, Chicago, IL 60611.
Key Words: Editorials • peptides • natriuretic peptides • heart failure
 |
Introduction |
|---|
 Top Introduction References |
|---|
Cardiac natriuretic peptides contribute importantly to the maintenance of sodium and volume homeostasis in health and disease. The hemodynamic, renal, and endocrinologic effects of these peptides have been the subject of intense basic and clinical investigation for more than 15 years. In particular, the activation of the cardiac natriuretic peptide system in patients with LV dysfunction has generated considerable interest recently, because elevated circulating levels of these substances have important prognostic and therapeutic implications. Unlike the vasoconstrictor neurohormones that are also activated in the setting of LV dysfunction, such as norepinephrine, the renin-angiotensin system, and arginine vasopressin, which play a pathogenetic role in the progression of ventricular dysfunction and development of heart failure, the cardiac natriuretic peptides have beneficial, compensatory actions to promote systemic arterial dilation, natriuresis, diuresis, and renin inhibition.
ANP is a 28–amino acid peptide synthesized and secreted by the atria.1 2 3 ANP is stored in the myocyte as a 126–amino acid prohormone. On secretion, the prohormone is split into an N-terminal moiety of 98 amino acids (N-ANP) and the biologically active ANP in equimolar amounts.3 N-ANP is more easily measured; it has a significantly longer half-life in plasma compared with ANP, which is very short lived (half-life, 2.5 minutes2 ) and thus has up to 50 times the plasma concentration of ANP.2 3 4 In addition, N-ANP is more stable under laboratory conditions for measurement.5
It is now well established that circulating ANP levels are increased in patients with chronic congestive heart failure in proportion to the severity of the disease4 6 7 8 and are elevated in patients with asymptomatic LV dysfunction.9 10 Although there is a relation between plasma ANP levels and atrial pressure, it is generally believed that atrial wall stress and stretch, rather than atrial pressure, are the predominant stimuli for ANP release.11 ANP is secreted in increased amounts from the ventricle as well as the atrium in patients with heart failure.8 12 Infusion of ANP in patients with heart failure results in reductions in right atrial and pulmonary artery wedge pressure, reduction in systemic vascular resistance, increased stroke volume, enhanced natriuresis and diuresis, and inhibition of both the renin-angiotensin system and the sympathetic nervous system.13 14 Thus, vasorelaxation and natriuresis are achieved without further activation of constrictor neurohormones. As a vasodilating agent without reflex sympathetic stimulation and a natriuretic agent without activation of the renin-angiotensin system, ANP raises intriguing possibilities for the treatment of heart failure.
BNP is a 32–amino acid peptide that is structurally similar to ANP and shares the same guanylate cyclase receptors on endothelial cells. Identified initially in porcine brain several years after the isolation of ANP, BNP was subsequently isolated from the cardiac tissue of many species, including humans.15 16 BNP is secreted predominantly from the ventricle in response to ventricular dilatation, although smaller amounts are also released from atrial myocytes.8 12 Circulating BNP levels are increased in patients with heart failure in proportion to the severity of the disease.8 Similar to the actions of ANP, infusion of BNP in patients with heart failure results in a reduction in preload and afterload, increased stroke volume, enhanced natriuresis and diuresis, and a reduction in aldosterone.17 Unlike ANP, BNP does not reduce norepinephrine levels but may actually increase norepinephrine via baroreceptor-mediated sympathetic discharge. Because ANP and BNP share common guanylate cyclase receptors, large amounts of intravenously administered BNP compete with ANP for these receptors and may increase circulating ANP levels despite the reduction in right and left atrial pressures.
Thus, ANP and BNP together form a dual, integrated natriuretic peptide system with important compensatory renal, cardiovascular, and endocrinologic actions in patients with heart failure. Of the two peptides, BNP has been studied less extensively. The articles by Omland et al18 and Clarkson et al19 in the current issue of Circulation add important new insights into the physiological effects and prognostic implications of BNP.
Omland et al18 address the potential role of plasma BNP in risk stratification of patients after acute myocardial infarction. The prognostic implications of ANP have been well established in patients with heart failure6 7 and in asymptomatic patients with LV dysfunction after myocardial infarction.20 21 22 23 24 25 26 Because circulating ANP levels are increased in heart failure in relation to the severity of heart failure and in parallel with the activation of other neurohormonal systems, the association of this cardiac natriuretic peptide with prognosis in patients with chronic heart failure is an important but not totally unexpected finding. Of further interest are the observations in several studies that plasma ANP and N-ANP are significantly elevated in asymptomatic patients with LV dysfunction, although less so than in patients with overt symptoms of heart failure.9 10 24 25 Thus, circulating ANP or N-ANP levels might be useful as markers to identify these asymptomatic patients. Moreover, in the SAVE study, the plasma ANP level, along with levels of other neurohormones, was a predictor of cardiac mortality and/or the development of heart failure in asymptomatic patients with LV dysfunction after acute myocardial infarction.24 In a multivariate analysis of the SAVE data, plasma renin activity and ANP were the only independent neurohormonal predictors of mortality. Similarly, in CONSENSUS II, plasma ANP after acute myocardial infarction was strongly related to subsequent cardiovascular mortality.26 However, in both the SAVE and CONSENSUS II trials, plasma ANP was also significantly associated with severity of LV dysfunction, and the independent predictive value of plasma ANP levels was markedly reduced or eliminated in multivariate analyses that included LV ejection fraction,24 26 which is firmly established as a powerful determinant of prognosis after myocardial infarction.27 Hence, once LV ejection fraction is known, measurement of plasma ANP or other neurohormones appears to add little to assessment of risk in patients after myocardial infarction. On the other hand, knowledge of ANP levels might be valuable in situations in which assessment of LV function is not available.
Subsequent data from the SAVE investigators, reported by Hall et al,25 demonstrated that N-ANP, perhaps owing to its higher plasma levels or greater ease of measurement than ANP, was a much stronger predictor of death and other cardiac end points after myocardial infarction than was ANP itself. N-ANP was also an independent predictor of outcome when considered in a multivariate model that included ejection fraction and other clinical variables and was actually a stronger predictor of cardiovascular death and heart failure than age, prior infarction, or ejection fraction. These data suggest that N-ANP provides prognostic information that is independent of and additive to LV ejection fraction in patients with acute myocardial infarction and challenge the concept that the only reason neurohormonal activation is an important prognostic variable is because it reflects the severity of underlying LV dysfunction.
BNP might be expected to be superior to ANP for risk assessment after myocardial infarction as well. BNP levels are considerably higher than ANP levels during the first hours of infarction, rising to levels 20 times those of ANP and 60 times those of normal levels.28 29 BNP, like N-ANP, is very stable under in vitro laboratory conditions and is measured relatively easily. BNP is released in increased amounts throughout the ventricular myocardium but principally from the infarct zone, presumably in response to increased regional wall stress.29 Hence, the magnitude of the elevation of plasma BNP is related to the size of the infarction, the severity of global LV dysfunction, or both,28 29 30 which should relate to prognosis. Some studies of chronic heart failure8 15 indicate that plasma BNP is elevated in proportion to the degree of LV dysfunction. On the other hand, other studies of chronic heart failure indicate that circulating BNP levels are less closely related to the magnitude of depression in ejection fraction than are ANP levels,4 which suggests that BNP might provide prognostic insights that are independent of the ejection fraction.
In their current study, Omland et al18 report for the first time that plasma BNP provides significant prognostic information in patients after acute myocardial infarction and that this information is indeed independent of the LV ejection fraction. Although ANP and N-ANP were also univariate predictors of subsequent cardiovascular death in this analysis, these atrial peptides were closely related to the ejection fraction, and only BNP provided additional prognostic power beyond that gained from measurement of ejection fraction. These data have important implications regarding current and future risk stratification and management strategies. It has already been suggested that measurement of plasma BNP may be a cost-effective means of identifying patients who are candidates for ACE inhibition after myocardial infarction,30 31 especially in situations in which measurement of ejection fraction is not possible.
The discordance between these current data and those of the SAVE
investigators25 regarding whether the prognostic value of
plasma N-ANP is independent of ejection fraction cannot be readily
explained but probably relates to differences in LV function between
the two study groups. The patient groups were similar in terms of age,
sex, Killip class, and percent who received
thrombolytic therapy during the acute phase and ACE
inhibitors during the chronic phase. However, it is
noteworthy that only 27 of the 79 patients studied by
echocardiography by Omland et al18 had
ejection fractions <45%. By study-entry criteria, all patients in
the SAVE trial had ejection fractions 
40%.25 Thus, the
ejection fractions differed significantly between the two studies
(mean, 31% in SAVE and 47% in the series by Omland et al).
Differences in baseline LV function between the two studies are further
underscored by the greater number of patients who developed transient
heart failure during the acute phase of infarction in SAVE (43%)
compared with patients in the study by Omland et al (29%). As ANP and
N-ANP levels are related to LV function, the wide range of ejection
fractions in patients studied by Omland et al would tend to accentuate
the dependence of N-ANP on ejection fraction to a greater extent than
in the SAVE patients. This possibly obscures any independent relation
between N-ANP and prognosis that might be operative in patients with
ejection fractions below 40% to 45%, while it accentuates the
independent relation between prognosis and BNP, which is less affected
by ejection fraction. The small sample of patients who underwent
echocardiography in the study by Omland et al,
especially the small number of patients with LV dysfunction, makes
definitive comparisons difficult. The relative values of BNP and N-ANP
in risk stratification in relation to both predictive accuracy and the
ease and cost of measurement must await additional, larger studies.
It is known that both ANP and BNP levels are markedly increased in patients with acute myocardial infarction at the time of hospital admission.21 22 28 ANP levels decrease thereafter, whereas BNP levels continue to rise and peak at 16 hours.28 In a subset of patients, BNP levels manifest a biphasic pattern, with a second peak at day 5. The biphasic pattern predominates in patients with anterior infarction, heart failure symptoms, greater creatine kinase–MB release, and lower ejection fractions.28 The late peak of BNP is presumably related to greater wall stress in such patients, which may be an early marker for subsequent LV remodeling. Thus, evaluation of the pattern of plasma BNP levels as a function of time should also be an important variable regarding subsequent prognosis. As the BNP data from Omland et al were obtained by use of a single blood sample at day 3, it is conceivable that a different timing of sampling or multiple samples might provide additional prognostic insights.
The second novel study investigating BNP in this issue of Circulation19 addresses the effects of BNP on exercise hemodynamics and exercise tolerance in patients with heart failure and normal LV systolic function. This is an intriguing and challenging subset of patients, who may account for up to 30% to 40% of patients with symptoms of heart failure. Although considerable attention has been focused on these patients over the past decade and a half and although great strides have been made in understanding the abnormalities in LV relaxation and compliance that may contribute to "diastolic" heart failure, therapeutic advances to date generally have been disappointing.
There are a number of factors that predispose to abnormalities in diastolic behavior of the ventricle and that lead to impaired forward output, elevated filling pressures, or both, despite normal systolic function. These include aging, hypertension, hypertrophy, ischemia, and fibrosis,32 33 and the majority of patients with this disordered physiology are elderly individuals with hypertension and LV hypertrophy. In theory, drugs that effectively lower blood pressure without activating neurohormones to stimulate further hypertrophy should be beneficial, and ß-blocking agents, calcium channel blockers, and ACE inhibitors are effective in many patients.33 34 35 36 However, in many others, such standard drug therapy is ineffective or only partially effective in the relief of symptoms.
It is known that many patients with normal systolic function but impaired diastolic relaxation and filling have inadequate utilization of Frank-Starling mechanisms during exercise that accounts for effort intolerance.37 38 39 The normal left ventricle augments cardiac output during the early phases of exercise via recruitment of preload reserve and chamber dilation.40 This is accomplished through increases in venous return from the exercising muscle beds and the combined lusitropic effects of enhanced contraction (resulting in greater elastic recoil or "restoring forces") and sympathetic nervous stimulation, which augment ventricular relaxation and allow the ventricle to fill to higher end-diastolic volumes without the price of higher end-diastolic pressures.40 These mechanisms are particularly important with aging, as the reduction in the chronotropic response to exercise requires greater reliance on contractile reserve and preload reserve to augment cardiac output at progressive workloads. In patients with heart failure and normal systolic function, particularly those with hypertension and hypertrophy, these normal responses to exercise are inadequate; either end-diastolic volume cannot be increased adequately to augment stroke volume or the increase in end-diastolic volume is associated with an exaggerated increase in end-diastolic pressure, which leads to symptoms of fatigue, dyspnea, or both.37 38 39
The study by Clarkson et al19 investigates the physiological and possible therapeutic effects of BNP administration in six patients with isolated diastolic heart failure with moderately severe exertional symptoms, five of whom had hypertension and four of whom had LV hypertrophy. During exercise, both pulmonary artery pressure and pulmonary capillary wedge pressure increased markedly. Plasma levels of both ANP and BNP were elevated beyond the normal range in these patients under baseline conditions, which is a noteworthy finding unto itself, as LV filling pressures were normal at rest and there is no definite evidence that hypertension alone is associated with elevation of circulating cardiac natriuretic peptides.41 This suggests that the repeated elevation of cardiac filling pressures during exercise may have been the stimulus for release of ANP and BNP. BNP administration resulted in a significant reduction in exercise-induced increase in pulmonary capillary wedge pressure and pulmonary artery pressure with no change in stroke volume. As in previous studies in patients with LV systolic dysfunction,17 BNP administration also resulted in a decrease in plasma aldosterone levels. The improved hemodynamics with BNP infusion during exercise are a unique observation that has the potential to represent a major step forward in the understanding of diastolic dysfunction and the role of cardiac natriuretic peptides in the regulation of diastolic as well as systolic function. This may also represent a new avenue for development of therapeutic strategies.
The major limitation of the study by Clarkson et al is the small number of patients, from which definitive conclusions cannot be reached. However, the small sample size is understandable given the tight patient selection criteria and the complexities of the invasive study design. A previous exercise hemodynamic study by Kitzman et al,38 widely regarded as one of the more important articles in this field in recent years, included only seven patients and did not require repeated testing with an investigational agent.
The mechanism of the hemodynamic effect of BNP in patients with diastolic dysfunction cannot be determined from the available data. LV relaxation is sensitive to afterload, and peripheral arterial vasodilation by BNP could increase the rate of relaxation. However, BNP did not alter blood pressure or systemic vascular resistance at rest or with exercise, which does not support this argument. The authors postulate that BNP may have a direct lusitropic effect on myocardial relaxation. Clearly, further investigation in this area is necessary to explore this possibility. The presence of ANP and BNP binding sites in the heart42 makes this a hypothesis worth testing. Such direct myocardial effects or effects on myocardial function mediated through the endothelium would have important therapeutic implications for patients with LV systolic as well as diastolic dysfunction.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Footnotes |
|---|
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
|
References |
|---|
|
TopIntroductionReferences |
|---|
1. de Bold AJ, Borenstein HB, Veress AT, Sonenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. 1981;28:89-94. [Medline] [Order article via Infotrieve]
2. Yandle TG, Richards AM, Nicholls MG, Cueno R, Espiner EA, Livesy JH. Metabolic clearance rate and plasma half-life of alfa-human atrial natriuretic peptide in man. Life Sci. 1986;38:1827-1833. [Medline] [Order article via Infotrieve]
3. Mathisen P, Hall C, Simonsen S. Comparative study of atrial peptides ANF(1-98) and ANF(99-126) as diagnostic markers of atrial distension in patients with cardiac disease. Scand J Clin Lab Invest. 1991;53:41-49.
4.
Wei CM, Heutlein DM, Perrella MA, Lerman A, Rodeheffer
RJ, McGregor CGA, Edwards WD, Schaff HV, Burnett JC.
Natriuretic peptide system in human heart failure.
Circulation. 1993;88:1004-1009.
5.
Nelesen RA, Dimsdale JE, Ziegler MG. Plasma
atrial natriuretic peptide is unstable under most storage
conditions. Circulation. 1992;86:463-468.
6. Gottlieb SS, Kukin ML, Ahern D, Packer M. Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure. J Am Coll Cardiol. 1989;13:1334-1339.
7.
Swedberg K, Eneroth P, Kjekshus J, Wilhelmsen
L. Hormones regulating cardiovascular function
in patients with severe congestive heart failure and their relation to
mortality. Circulation. 1990;82:1730-1736.
8.
Yasue H, Yoshimura M, Sumida H, Kikuta K, Kugiyama K,
Jougasaki M, Ogawa H, Okumura K, Mukoyama M, Nakao K.
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.
9.
Francis GS, Benedict C, Johnstone DE, Kirlin PC,
Nicklas J, Liang C, Kubo SH, Rudin-Toretsky E, Yusuf S.
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). Circulation. 1990;82:1724-1729.
10. Lerman A, Gibbons RJ, Rodeheffer RJ, Bailey KB, McKinley LJ, Heublein DM, Burnett JC. Circulating N-terminal atrial natriuretic peptide as a marker for symptomless left-ventricular dysfunction. Lancet. 1993;341:1105-1109. [Medline] [Order article via Infotrieve]
11.
Edwards BS, Zimmerman RS, Schwab TR, Heublein DM,
Burnett JC. Atrial stretch, not pressure, is the principal
determinant controlling the acute release of atrial
natriuretic peptide. Circ Res. 1988;62:191-195.
12.
Yoshimura M, Yasue H, Okumura K, Ogawa H, Jougasaki M,
Mukoyama M, Nakao K, Imura H. Different secretion patterns of
atrial natriuretic peptide and brain
natriuretic peptide in patients with congestive heart
failure. Circulation. 1993;87:464-469.
13.
Saito Y, Nakao K, Nishimura K, Sugawara A, Okumura K,
Obata K, Sonoda R, Ban T, Yasue H, Imura H. Clinical application
of atrial natriuretic polypeptide in patients with
congestive heart failure: beneficial effects on left
ventricular function.
Circulation. 1987;76:115-124.
14. Molina CR, Fowler MB, McCrory S, Peterson C, Myers BD, Schroeder JS, Murad F. Hemodynamic, renal, and endocrine effects of atrial natriuretic peptide infusion in severe heart failure. J Am Coll Cardiol. 1988;12:175-186. [Abstract]
15. Mukoyama M, Nakao K, Saito Y, Ogawa Y, Hosoda K, Suga S, Shirakami G, Jougasaki M, Imura H. Increased human brain natriuretic peptide in congestive heart failure. N Engl J Med. 1990;323:757-758. [Medline] [Order article via Infotrieve]
16. Mukoyama M, Nakao K, Hosoda K, Suga S, Saito Y, Ogawa Y, Shirakami G, Jougasaki M, Obata K, Yasue H, Kambayashi Y, Inouye K, Imura H. Brain natriuretic peptide (BNP) as a novel cardiac hormone in humans: evidence for an exquisite dual natriuretic peptide system. J Clin Invest. 1991;87:1402-1412.
17.
Yoshimura M, Yasue H, Morita E, Sakaino N, Jougasaki M,
Kurose M, Mukoyama M, Saito Y, Okumura K, Nakao K, Imura H.
Hemodynamic, renal, and hormonal responses to brain
natriuretic peptide infusion in patients with congestive
heart failure. Circulation. 1991;84:1581-1588.
18.
Omland T, Aakvaag A, Bonarjee VVS, Caidahl K, Lie RT,
Nilsen DWT, Sundsfjord JA, Dickstein K. Plasma brain
natriuretic peptide as an indicator of left
ventricular systolic function and long-term
survival after acute myocardial infarction: comparison with plasma
atrial natriuretic peptide and N-terminal proatrial
natriuretic peptide.
Circulation. 1996;93:1963-1969.
19.
Clarkson PBM, Wheeldon NM, MacFadyen RJ, Pringle SD,
MacDonald TM. Effects of brain natriuretic peptide
on exercise hemodynamics and neurohormones in isolated
diastolic heart failure.
Circulation. 1996;93:2037-2042.
20. Tan ACITL, van Loenhout T, Lamfers EJP, Hooghoudt TEH, Kloppenborg PWC, Benrand TJ. Atrial natriuretic peptide after myocardial infarction. Am Heart J. 1989;118:490-493. [Medline] [Order article via Infotrieve]
21. Jougasaki M, Yasue H, Mukoyama M, Nakao K, Takahashi K. Appearance of atrial natriuretic peptide in the ventricles in patients with myocardial infarction. Am Heart J. 1990;119:92-96. [Medline] [Order article via Infotrieve]
22.
Svanegaard J, Angelo-Nielson K, Pindborg T.
Plasma concentration of atrial natriuretic peptide at
admission and risk of cardiac death in patients with acute myocardial
infarction. Br Heart J. 1992;68:38-42.
23.
Omland T, Bonarjee VVS, Nilsen DWT, Sundsfjord JA, Lie
RT, Thibault G, Dickstein K. Prognostic significance of
N-terminal pro-atrial natriuretic factor (1-98) in
acute myocardial infarction: comparison with atrial
natriuretic factor (99-126) and clinical
evaluation. Br Heart J. 1993;70:409-414.
24. Rouleau JL, Packer M, Moye L, de Champlain D, Bichet D, Klein M, Rouleau J, Sussex B, Arnold MG, Sestier F, Parker JO, McEwan P, Bernstein V, Cuddy TE, Lamas GA, Gottlieb SS, McCans J, Nadeau C, Delage F, Wun CC, Pfeffer MA. Prognostic value of neurohumoral activation in patients with an acute myocardial infarction: effect of captopril. J Am Coll Cardiol. 1994;24:583-591. [Abstract]
25.
Hall C, Rouleau JL, Moye L, de Champlain D, Bichet D,
Klein M, Sussex B, Packer M, Rouleau J, Arnold MG, Lamas GA, Sestier F,
Gottlieb SS, Wun CC, Pfeffer MA. N-terminal proatrial
natriuretic factor: an independent predictor of
long-term prognosis after myocardial infarction.
Circulation. 1994;89:1934-1942.
26. Omland T, Bonarjee VVS, Lie RT, Caidahl K. Neurohumoral measurements as indicators of long-term prognosis after acute myocardial infarction. Am J Cardiol. 1995;76:230-235. [Medline] [Order article via Infotrieve]
27. The Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med. 1983;331:309-336.
28.
Morita E, Yasue H, Yoshimura M, Ogawa H, Jougasaki M,
Matsumura T, Mukoyama M, Nakao K. Increased plasma levels of
brain natriuretic peptide in patients with acute myocardial
infarction. Circulation. 1993;88:82-91.
29. Sumida H, Yasue H, Yoshimura M, Okumura K, Ogawa H, Kugiyama K, Matsuyama K, Kikuta K, Morita E, Nakao K. Comparison of secretion pattern between A-type and B-type natriuretic peptides in patients with old myocardial infarction. J Am Coll Cardiol. 1995;25:1105-1110. [Abstract]
30. Motwani JG, McAlfine H, Kennedy N, Struthers AD. Plasma brain natriuretic peptide as an indicator for angiotensin-converting-enzyme inhibition after myocardial infarction. Lancet. 1993;341:1109-1113. [Medline] [Order article via Infotrieve]
31.
Choy AMJ, Darbar D, Lang CC, Pringle TH, McNeill GP,
Kennedy NSJ, Struthers AD. Detection of left
ventricular dysfunction after acute myocardial infarction:
comparison of clinical, echocardiographic, and
neurohormonal methods. Br Heart J. 1994;72:16-22.
32. Grossman W. Diastolic dysfunction in congestive heart failure. N Engl J Med. 1992;325:1557-1564. [Medline] [Order article via Infotrieve]
33. Bonow RO, Udelson JE. Left ventricular diastolic dysfunction as a cause of congestive heart failure: mechanisms and management. Ann Intern Med. 1992;117:502-510.
34. Schulman SP, Weiss JL, Becker LC, Gottlieb SO, Woodruff KM, Weisfeldt ML, Gerstenblith G. The effects of antihypertensive therapy on left ventricular mass in elderly patients. N Engl J Med. 1990;322:1350-1356. [Abstract]
35. Setaro J, Zaret BL, Schulman DS, Soufer R. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic performance. Am J Cardiol. 1990;66:981-986. [Medline] [Order article via Infotrieve]
36. Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH. Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload hypertrophy: effects on coronary resistance, contractility, and relaxation. J Clin Invest. 1990;86:1913-1920.
37.
Cuocolo A, Sax FL, Brush JE, Maron BJ, Bacharach SL,
Bonow RO. Left ventricular hypertrophy
and impaired diastolic filling in essential hypertension:
diastolic mechanisms for systolic dysfunction
during exercise. Circulation. 1990;81:978-986.
38. Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol. 1991;17:1065-1072. [Abstract]
39. Sobue T, Yokota M, Iwase M, Ishihara H. Influence of left ventricular hypertrophy on left ventricular function during dynamic exercise in the presence or absence of coronary artery disease. J Am Coll Cardiol. 1995;25:91-98. [Abstract]
40. Bonow RO. Left ventricular response to exercise. In: Fletcher GF, ed. Cardiovascular Response to Exercise. Mt Kisco, NY: Futura Publishing Co, Inc; 1993:31-47. American Heart Association Monograph Series.
41. Hollister AS, Inagami T. Atrial natriuretic factor and hypertension: a review and meta-analysis. Am J Hypertens. 1991;4:850-865. [Medline] [Order article via Infotrieve]
42. Oehlenschlager WF, Baron PA, Schomer H, Currie MC. Atrial and brain natriuretic peptides share binding sites in the kidney and the heart. Eur J Pharmacol. 1989;161:159-164.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  G. Mercuro, C. Cadeddu, A. Piras, M. Dessi, C. Madeddu, M. Deidda, R. Serpe, E. Massa, and G. Mantovani Early Epirubicin-Induced Myocardial Dysfunction Revealed by Serial Tissue Doppler Echocardiography: Correlation with Inflammatory and Oxidative Stress Markers Oncologist, September 1, 2007; 12(9): 1124 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Qian, A. Leung, P. Harding, and M. C. LaPointe PGE2 stimulates human brain natriuretic peptide expression via EP4 and p42/44 MAPK Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1740 - H1746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lev-Sagie, B. Bar-Oz, L. Salpeter, D. Hochner-Celnikier, I. Arad, and A. Nir Plasma Concentrations of N-Terminal Pro-B-Type Natriuretic Peptide in Pregnant Women near Labor and during Early Puerperium Clin. Chem., October 1, 2005; 51(10): 1909 - 1910. [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Sun, C. Dominguez, N. A. Mallavaram, and J. M. Quaegebeur Dysfunction of atrial and B-type natriuretic peptides in congenital univentricular defects J. Thorac. Cardiovasc. Surg., May 1, 2005; 129(5): 1104 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Vanderheyden, M. Goethals, S. Verstreken, B. De Bruyne, K. Muller, E. Van Schuerbeeck, and J. Bartunek Wall stress modulates brain natriuretic peptide production in pressure overload cardiomyopathy J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2349 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Suzuki, M. Yoshimura, M. Nakayama, Y. Mizuno, E. Harada, T. Ito, S. Nakamura, K. Abe, M. Yamamuro, T. Sakamoto, et al. Plasma Level of B-Type Natriuretic Peptide as a Prognostic Marker After Acute Myocardial Infarction: A Long-Term Follow-Up Analysis Circulation, September 14, 2004; 110(11): 1387 - 1391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ruskoaho Cardiac Hormones as Diagnostic Tools in Heart Failure Endocr. Rev., June 1, 2003; 24(3): 341 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Jernberg, M. Stridsberg, P. Venge, and B. Lindahl N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation J. Am. Coll. Cardiol., August 7, 2002; 40(3): 437 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Suzuki, T. Yamazaki, and Y. Yazaki The role of the natriuretic peptides in the cardiovascular system Cardiovasc Res, August 15, 2001; 51(3): 489 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. He, D. Wang, X.-P. Yang, O. A. Carretero, and M. C. LaPointe Inducible regulation of human brain natriuretic peptide promoter in transgenic mice Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H368 - H376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Iivainen, K. W.E. Groundstroem, J. T. Lahtela, T. J. Talvensaari, A. Pasternack, and A. Uusitalo Serum N-terminal atrial natriuretic peptide in adult patients late after surgical repair of atrial septal defect Eur J Heart Fail, June 1, 2000; 2(2): 161 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kataoka and S. Takada The role of thoracic ultrasonography for evaluation of patients with decompensated chronic heart failure J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1638 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Langenickel, I. Pagel, K. Hohnel, R. Dietz, and R. Willenbrock Differential regulation of cardiac ANP and BNP mRNA in different stages of experimental heart failure Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1500 - H1506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. WILLENBROCK, I. PAGEL, M. SCHEUERMANN, K. HÖHNEL, H. S. MACKENZIE, B. M. BRENNER, and R. DIETZ Renal Function in High-Output Heart Failure in Rats: Role ofEndogenous Natriuretic Peptides J. Am. Soc. Nephrol., March 1, 1999; 10(3): 572 - 580. [Abstract] [Full Text]
|
|
|
|
|
|
M. L Kuroski de Bold Estrogen, natriuretic peptides and the renin-angiotensin system Cardiovasc Res, March 1, 1999; 41(3): 524 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Richards, M G Nicholls, T G Yandle, H Ikram, E A Espiner, J G Turner, R C Buttimore, J G Lainchbury, J M Elliott, C Frampton, et al. Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction Heart, February 1, 1999; 81(2): 114 - 120. [Abstract] [Full Text]
|
|
|
|
|
|
K.-B. Kim, C.-H. Lee, C.-H. Kim, Y.-J. Cha, S. :, and J. L. Cox Effect of the Cox maze procedure on the secretion of atrial natriuretic peptide J. Thorac. Cardiovasc. Surg., January 1, 1998; 115(1): 139 - 147. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||