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Franz-Volhard-Clinic, Max-Delbrück-Center for Molecular Medicine, University Hospital Charité, Humboldt-University of Berlin, 13125 Berlin, Germany
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones that are involved in water and electrolyte homeostasis in heart failure. Although both hormones exert almost identical biological actions, the differential regulation of cardiac ANP and BNP mRNA in compensated and overt heart failure is not known. To study the hypothesis that cardiac BNP is more specifically induced in overt heart failure, a large aortocaval shunt of 30 days duration was produced in rats and compared with compensated heart failure. Compensated heart failure was induced either by a small shunt of 30 days duration or by a large shunt of 3 days duration. Both heart failure models were characterized by increased cardiac weight, which was significantly higher in the large-shunt model, and central venous pressure. Left ventricular end-diastolic pressure was elevated only in the overt heart failure group (control: 5.7 ± 0.7; small shunt: 8.6 ± 0.9; large shunt 3 days: 8.5 ± 1.7; large shunt 30 days: 15.9 ± 2.6 mmHg; P < 0.01). ANP and BNP plasma concentrations were elevated in both heart failure models. In compensated heart failure, ANP mRNA expression was induced in both ventricles. In contrast, ventricular BNP mRNA expression was not upregulated in any of the compensated heart failure models, whereas it increased in overt heart failure (left ventricle: 359 ± 104% of control, P < 0.001; right ventricle: 237 ± 33%, P < 0.01). A similar pattern of mRNA regulation was observed in the atria. These data indicate that, in contrast to ANP, cardiac BNP mRNA expression might be induced specifically in overt heart failure, pointing toward the possible role of BNP as a marker of the transition from compensated to overt heart failure.
atrial natriuretic peptide; brain natriuretic peptide; gene expression; aortocaval shunt
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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THE NATRIURETIC PEPTIDES are a family of three genetically distinct peptide hormones: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). CNP is synthesized in high concentrations in the brain (34) and endothelium (35), and only minor amounts can be detected in atria or ventricles (38). Even though BNP was first described in the mammalian brain (33), ANP and BNP are mainly synthesized in the heart. Under physiological conditions, ANP is synthesized in the atria (11), whereas BNP is produced by atrial and ventricular cardiomyocytes (24, 42). The BNP mRNA expression is more than twofold higher in atria than in ventricles, but the BNP production in the ventricles is considered more important for the contribution to BNP plasma concentrations due to the larger mass of the ventricles (26).
The main actions of ANP and BNP include natriuresis, diuresis, and inhibition of the renin-angiotensin-aldosterone system (6, 26). In heart failure, plasma concentrations of ANP and BNP are elevated (39). Both peptides become important to counteract the water and sodium retention and to decrease the peripheral vasoconstriction, which are induced in heart failure by an activated renin-angiotensin-aldosterone system and by vasopressin (5). When plasma concentrations were compared, BNP had been shown to be increased earlier than ANP in states of acute severe heart failure, giving rise to the concept of BNP as an emergency hormone (16, 21).
In a genetic model of hypertension in the rat (3), in chronic volume overloaded rats (13, 23), in cardiomyopathic hamsters (12), in pacing-induced canine heart failure (30), and in autopsy samples of patients with congestive heart failure (32), the ventricles are recruited to synthesize ANP and contribute to the elevated ANP plasma concentrations. Compared with ANP, plasma concentrations of BNP were shown to be a better marker for impaired left ventricular function (22) and to be of higher prognostic value in heart failure (29, 41).
Previous studies demonstrated that cardiac BNP mRNA was induced in heart failure. In pacing-induced canine heart failure, cardiac BNP mRNA expression was enhanced, but ANP mRNA was not measured in that study (24). In terminal human heart failure, BNP and ANP mRNA in cardiac tissue from explanted hearts were elevated in parallel (36). These results suggested an increased cardiac BNP synthesis in severe heart failure. To the best of our knowledge, no studies have been performed so far to compare the induction of ANP and BNP mRNA in both ventricles during the transition from compensated to overt heart failure. It is still unclear whether the ventricular recruitment of BNP is specific for overt heart failure and whether ANP mRNA is induced in early stages and in compensated heart failure when BNP mRNA is still unchanged. To test the hypothesis that cardiac BNP mRNA expression is specifically induced only in severe heart failure, we analyzed atrial and ventricular ANP and BNP mRNA expression in different stages and degrees of experimental heart failure.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Animals. Male Wistar rats (230-250 g) from Moellegaard Animal Farms (Schoenwalde, Germany) were fed normal rat chow and were allowed free access to tap water. The animals were maintained on a 12:12-h light-dark cycle. All experiments were performed between 0700 and noon. The studies were approved by the local authorities and were performed according to the Guiding Principles in the Care and Use of Animals corresponding to American Physiological Society guidelines. Experiments were performed with 10-12 animals in each group.
Shunt operation. The aortocaval shunt was induced under ether anesthesia by a modification of the method developed by Garcia and Diebold (15). Briefly, a laparotomy was performed, and the aorta was punctured distal to the renal arteries with a 1.2-mm (outside diameter) disposable needle (Braun Melsungen, Melsungen, Germany) for the small shunt and with a 1.8-mm disposable needle for the large shunt. The needle was advanced in the adjacent inferior vena cava. After the aorta had been temporarily clamped, the needle was withdrawn, and the puncture site was sealed with cyanoacrylate glue (Instant Krazy Glue; Borden, Willowdale, Ontario, Canada). The persistence of the shunt was verified visually by swelling of the vena cava. The perioperative mortality was <3% in the small-shunt group and <5% in the large-shunt group. In sham-operated control rats, a laparotomy was performed, the vessels were dissected free of the surrounding tissue, but no puncture of the vessels was performed.
Hemodynamic measurements. Thirty days after induction of either small or large shunt or sham operation and 3 days after induction of large shunt or sham operation, a PE-50 tubing catheter was inserted in the right carotid artery under chloralhydrate anesthesia (400 mg/kg sc) for measurement of the mean arterial pressure (MAP). The catheter was then advanced in the left ventricle for measurement of end-diastolic pressure (LVEDP). Central venous pressure (CVP) was measured by cannulating the right atrium via the right jugular vein. All pressures were registered with a Statham transducer (P23XL) and a Gould AMP 4600 amplifier. Left ventricular contractility was obtained from the left ventricular pressure curves, which were converted with a Gould differentiator (G4615). Heart rate was derived from the arterial blood pressure signal.
Determination of ANP and BNP plasma concentrations.
Blood samples for ANP and BNP determinations were withdrawn from the
aorta in Na- and EDTA-preloaded (final concentration 7 mM) and
prechilled tubes. The blood was centrifuged at 4°C at 2,000 g for 10 min immediately after withdrawal, and the plasma was
maintained at 
80°C until extraction. ANP and BNP plasma
samples were extracted using C18 Sep-Pak columns that had
been equilibrated with acetonitrile and ammonium acetate (0.2%, pH
4.0). After plasma loading, the columns were washed with ammonium
acetate, and ANP and BNP were eluted with acetonitrile (60%)-ammonium
acetate (40%), following a previously described procedure (17). The
recovery for both peptides was ~80% and was taken into account when
the plasma values were calculated. Samples were then measured by RIA (17), which was performed with ANP antibodies kindly provided by Dr. J. Gutkowska (Montreal, Canada). BNP plasma concentrations were measured
with a commercially available kit (Peninsula, Paesel und Lorei, Hanau, Germany).
RNA analysis.
Under chloralhydrate anesthesia (400 mg/kg sc), the entire heart was
rapidly removed, rinsed in RNase-free NaCl (0.9%, 4°C), and
weighed. The atria were dissected from the ventricles. To not
contaminate ventricular tissue with atrial tissue and vice versa,
special care was taken, and the ventricular tissue was separated
distinctly from the atria. The remaining tissue (including the valvular
areas and the septum) was discarded. The tissue parts were weighed and
rapidly frozen in liquid nitrogen and were stored at 80°C
until RNA extraction. RNA was isolated according to the method
described by Chomczynski and Sacchi (9). In brief, tissues were
homogenized in guanidinium thiocyanate solution (pH 7.4) and extracted
by addition of phenol/chloroform. RNA from the aqueous phase was
precipitated by addition of 
vol of 4.0 M sodium acetate (pH
5.2) and 2.5 vol of ethanol. After centrifugation, the pellet obtained
was dissolved in 30 µl of diethyl pyrocarbonate-treated water. The
concentration of isolated RNA was determined spectrophotometrically at
260 nm wavelength. RNA (15 µg) was either loaded on a 1.2% agarose
gel for subsequent Northern blotting or was directly transferred in the
slot-blot apparatus for blotting on a nylon membrane (Hybond
N+ Nucleic Acid Transfer Membrane; Amersham). The cDNA
probes for ANP, BNP, and glyceraldehyde-3-phosphate
dehydrogenase (GAPDH) were synthesized by PCR with specific primer
pairs (ANP: Ar-CTGCTAGACCACCTGGAGGAG/Br-CCAGGAGGGTATTCACCA- CCAC;
BNP: Ar-CACTTCTGCAGCATGGATCTCCAGAAG/Br-GTGGTCCCAGAGCTGGGGAAAGAAGAG; GAPDH: Ar-CCATGGAGAAGGCTGGGG/Br-CAAAGTTGTCATGGATG- ACC;
Biometra, Göttingen, Germany) and were labeled with
digoxigenin using the DIG DNA Labeling and Detection Kit
(Boehringer-Mannheim). After hybridization for 20 h at 42°C with
the specific probes, the mRNA was detected by chemiluminescence and
exposure to an X-ray film. To control for the amount of RNA loaded on
the gels and the slot-blot apparatus, all membranes were rehybridized
with the GAPDH probe. All results were normalized to the GAPDH mRNA
expression. One RNA sample of each tissue (left and right atria and
ventricles) of each animal was measured.
Statistical analysis. Differences between the groups were evaluated with the ANOVA and post hoc analysis (Fisher). The significance level was set at P < 0.05. All data are expressed as means ± SE.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Heart and lung weights and hemodynamic characterization of rats with
aortocaval shunt.
Total and relative heart weights, as well as the weights of all four
heart chambers, were elevated in rats with small shunt and increased
further in rats with a large shunt of 30 days duration (Table
1). The lung weights were unchanged in
animals with small shunt and increased by ~60% in rats 30 days after
large shunt, indicating pulmonary congestion. The MAP was decreased in
rats with small or large aortocaval shunt.
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ANP and BNP plasma concentrations.
ANP plasma concentrations were elevated approximately threefold in rats
with small shunt compared with controls and increased further in rats
with large shunt (Table 2). Similarly, BNP
plasma concentrations were elevated in animals with small shunt and
were significantly higher in rats with large shunts compared with
controls and rats with small shunt.
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Ventricular ANP and BNP mRNA expression.
Figure 2 shows a typical Northern blot
(using a slot-blot apparatus) of three samples of three left ventricles
of either controls or rats with small or large shunt, which were
hybridized with either ANP (Fig. 2A) or BNP probes (Fig.
2B). Left ventricular ANP mRNA expression was induced
approximately fivefold in rats with small shunt (Fig.
3A) and in rats after 3 days of
large shunt. The elevation of left ventricular ANP mRNA in rats after
30 days of large shunt did not exceed the levels observed after 30 days of small shunt. In contrast to ANP mRNA, the left ventricular BNP mRNA
expression was unchanged in rats with small shunt and after 3 days of
large shunt, whereas it increased significantly in rats after 30 days
of large shunt (Fig. 3B).
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0.001), 334 ± 46% of controls (large shunt/3 days, P 0.001), and 361 ± 38% of control (large shunt/30 days, P 0.001).
Similar to the data obtained when mRNA expression was normalized to
GAPDH, BNP mRNA expression was induced only in the large-shunt/30 days model (285 ± 47%, P 0.01 vs. control and vs. small shunt).
Atrial ANP and BNP mRNA expression. Left atrial ANP mRNA expression was increased in rats with small shunt and increased further in rats with large shunt (Table 3). In the right atrium, ANP mRNA was not specifically induced in any shunt model. BNP mRNA expression in both atria was unchanged in the small-shunt model and was enhanced only in rats with large shunt (Table 3).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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This study was designed to test the hypothesis that the cardiac BNP gene expression is specifically induced only in states of severe heart failure. Therefore, we analyzed cardiac mRNA at different time points and in different degrees of heart failure. In both ventricles and atria, a specific BNP mRNA induction occurred only in the large-shunt model after 30 days (when cardiac hypertrophy was further increased and pulmonary congestion, elevated end-diastolic pressures, and decreased cardiac contractility were present), indicating overt heart failure. These data suggest that the cardiac BNP mRNA induction is specifically induced in severe heart failure. In contrast, the cardiac ANP mRNA expression is less dependent on the severity of heart failure and is already induced in compensated heart failure, when hypertrophy occurred, but LVEDP was still normal.
Heart failure was created by an infrarenal aortocaval shunt, an established model of volume overload-induced heart failure (14, 20). The use of two different shunt sizes allowed the creation of either compensated or overt heart failure. In addition, the large-shunt model was analyzed 3 days after shunt induction, when no overt heart failure was present. Hemodynamic characterization showed only a slight increase in CVP and no increase in LVEDP in the small-shunt model and after 3 days of large shunt. In contrast, the large-shunt model after 30 days demonstrated the typical characteristics of overt heart failure, such as decreased cardiac contractility, elevated LVEDP, and an increased lung weight as an indicator of pulmonary congestion. The large-shunt model after 30 days demonstrated a significantly higher degree of cardiac hypertrophy compared with the small-shunt model or the large shunt after 3 days. Thus our model does not rule out the possibility that a severe degree of cardiac hypertrophy might have been induced by the molecular changes observed.
It has previously been shown that ventricular ANP mRNA was increased in heart failure (23, 32, 40). Ventricular BNP mRNA expression after severe pressure overload was induced faster than ANP mRNA (1). Similarly, after an acute massive myocardial stress induced by experimental myocardial infarction, BNP mRNA was induced within a few hours and was faster than ANP mRNA (18). The fact that BNP mRNA is upregulated very early in response to an adequate stimulus might be due to either two different mechanisms and two peaks of BNP mRNA induction. Alternatively, and supported by our data, BNP mRNA induction might require a stronger stimuli than necessary for induction of the ANP mRNA expression.
When plasma concentrations were compared, BNP has been shown to be
induced earlier than ANP in states of acute, severe heart failure,
giving rise to the concept of BNP as an emergency hormone (16, 21). Our
data demonstrate a dissociation between increased BNP plasma
concentrations and unchanged ventricular BNP mRNA expression in the
compensated heart failure models. It was recently reported that
-adrenergic stimulation of cardiomyocytes increased the half-life of
BNP mRNA up to fivefold via activation of mitogen-activated protein
kinase and protein kinase C (19). Although not investigated in this
study, an increased BNP mRNA stability in cardiomyocytes might have led
to increased BNP plasma concentrations in the small-shunt model without
enhancing the transcription rate. A different translation rate could be
an alternate explanation for the observed discrepancy between increased
BNP plasma concentrations and unaffected mRNA expression.
In this study, we compared the mRNA expression of both peptides in different degrees of heart failure. In compensated heart failure, either induced by a small aortocaval shunt or by a large shunt with only 3 days duration, left and right ventricular ANP mRNA expressions were elevated, indicating that already a slightly impaired ventricular function was a powerful stimulus for ANP mRNA induction. In overt heart failure, no further induction of ANP mRNA occurred. Although it was not the aim of this study to investigate the reason for the lack of further induction of ventricular ANP mRNA, our data are compatible with an autoregulatory negative feedback mechanism of ANP on its own gene expression, similarly to an autoregulatory mechanism that has been described for the regulation of ANP release (27).
In contrast to ANP, left and right ventricular BNP mRNA expression was not induced in compensated heart failure, indicating that stronger stimuli, like elevated end-diastolic pressure or enhanced ventricular wall stress, might be required. In overt heart failure, ventricular BNP mRNA was significantly increased, suggesting a different regulation of ventricular BNP mRNA in severe heart failure. These data are in agreement with a previous study in pacing-induced heart failure describing no change in left ventricular BNP mRNA in early left ventricular dysfunction and an increase in overt heart failure (24). No ANP mRNA was measured in that report. Therefore, to the best of our knowledge, this is the first report describing the specific induction of ventricular BNP, in contrast to ANP, in severe heart failure.
Even though the specific induction of cardiac BNP mRNA during the transition from compensated to overt heart failure has not been compared previously with the induction of cardiac ANP mRNA, our results are in agreement with reports on the regulation of plasma concentrations of ANP and BNP. Previous reports described ANP and BNP plasma concentrations as a useful marker of impaired ventricular function (37, 41). BNP plasma concentrations have been suggested as an indicator of poor prognosis after myocardial infarction (4, 29, 31), but the prognostic usefulness remains to be established (2; for review, see Ref. 7). The value of BNP plasma concentrations as a diagnostic marker for heart failure has also been described (10), and BNP has been demonstrated to be a more specific marker of left ventricular hypertrophy than ANP (22). In addition, BNP has been suggested as a marker of ventricular overload, whereas ANP was proposed to be more specifically released in response to atrial overload (43). The specific cardiac recruitment of BNP in overt heart failure, which is described in the present study, might contribute to the superiority of BNP plasma concentrations as a prognostic and diagnostic marker in heart failure compared with ANP.
In vitro studies in neonatal ventricular cardiomyocytes indicated that ANP and BNP gene expressions are regulated by distinct mechanisms (28). In studies with isolated hearts, the induction of BNP mRNA was faster (28), responded more to stretch (25), and was inducible to a greater degree after stimulation with endothelin (8) compared with ANP. In the present study, ventricular BNP expression was selectively induced in overt heart failure, indicating that a stronger stimulus was required for induction of BNP mRNA than for ANP mRNA. Ventricular stretch or excessive hypertrophy might be a possible candidate for the specific induction of BNP mRNA in overt heart failure animals. Other regulatory mechanisms, like neurohumoral interactions (endothelin, angiotensin) or local hypoxia due to diminished coronary flow, are alternative mechanisms for the induction of cardiac BNP mRNA in overt heart failure. Previous reports proposed the role of BNP as a fast, emergency hormone because of its rapid activation compared with ANP (18). The present study demonstrates that cardiac BNP mRNA was induced only in overt heart failure, suggesting a possible protective function of BNP in severe heart failure. Although not tested in this study, the ventricular synthesis of BNP might be a late compensatory mechanism in severe cardiac failure, and its biological effects might delay further decompensation. The biological profile of BNP with its natriuretic and vasodilating properties is compatible with the idea that the observed cardiac BNP gene expression might be a consequence rather than the cause of severe heart failure. However, BNP mRNA induction and elevation of BNP plasma concentrations did not successfully lead to an improvement of severe heart failure, nor did it prevent its occurrence. Therefore, BNP might not be an efficient compensatory hormone. This alternate hypothesis would limit the importance of BNP in severe heart failure to a marker of this disease state. The analysis of the functional importance of BNP, which was not the aim of the present study, warrants further investigation.
In conclusion, ventricular ANP mRNA expression was induced already in compensated heart failure, whereas the hemodynamic deterioration occurring in overt heart failure did not lead to any further induction of ventricular ANP mRNA. In contrast, cardiac BNP mRNA expression was elevated specifically in overt heart failure. These results suggest that cardiac BNP mRNA expression might be a more specific marker of overt heart failure compared with ANP.
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ACKNOWLEDGEMENTS |
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We are grateful to Astrid Schiche, Jeannette Mothes, and Rita Günzel for excellent technical assistance and secretarial help. We thank M. Scheuermann (Berlin, Germany) for critically reviewing the manuscript.
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FOOTNOTES |
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This project is supported by a grant from the Deutsche Forschungsgemeinschaft to R. Willenbrock (Wi 814/7-1).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: R. Willenbrock, Franz-Volhard-Klinik, Wiltbergstraße 50, 13125 Berlin, Germany (E-mail: willenbrock{at}fvk-berlin.de).
Received 26 January 1999; accepted in final form 1 December 1999.
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REFERENCES |
|---|
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Adachi, S,
Ito H,
Ohta Y,
Tanaka M,
Ishiyama S,
Nagata M,
Toyozaki T,
Hirata Y,
Marumo F,
and
Hiroe M.
Distribution of mRNAs for natriuretic peptides in RV hypertrophy after pulmonary arterial banding.
Am J Physiol Heart Circ Physiol
268:
H162-H169,
1995
2.
Anker, SD,
and
Coats AJS
Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction.
Circulation
95:
538-538,
1997.
3.
Arai, H,
Nakao K,
Saito Y,
Morii N,
Sugawara A,
Yamada T,
Itho H,
Shiono S,
Mukoyama M,
Ohkubo H,
Nakanishi S,
and
Imura H.
Augmented expression of atrial natriuretic polypeptide gene in ventricles of spontaneously hypertensive rats (SHR) and SHR-stroke prone.
Circ Res
62:
926-930,
1988
4.
Arakawa, N,
Nakamura M,
Aoki H,
and
Hiramori K.
Plasma brain natriuretic peptide concentrations predict survival after acute myocardial infarction.
J Am Coll Cardiol
27:
1656-1661,
1996[Abstract].
5.
Arnolda, L,
McGrath BP,
and
Johnston CI.
Vasopressin and angiotensin II contribute equally to the increased afterload in rabbits with heart failure.
Cardiovasc Res
25:
68-72,
1991
6.
Awazu, M,
and
Ichikawa I.
Biological significance of atrial natriuretic peptide in the kidney.
Nephron
63:
1-14,
1993[Web of Science][Medline].
7.
Bonow, RO.
New insights into the cardiac natriuretic peptides.
Circulation
93:
1946-1950,
1996
8.
Bruneau, BG,
and
de Bold AJ.
Selective changes in natriuretic peptide A and early response gene expression in isolated rat atria following stimulation by stretch or endothelin-1.
Cardiovasc Res
28:
1519-1525,
1994[Web of Science][Medline].
9.
Chomczynski, P,
and
Sacchi N.
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
Anal Biochem
162:
156-159,
1987[Web of Science][Medline].
10.
Cowie, MR,
Struthers AD,
Wood DA,
Coats AJS,
Thompson SG,
and
Poole-Wilson PA.
Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care.
Lancet
350:
1347-1351,
1997.
11.
de Bold, AJ.
Atrial natriuretic factor: a hormone produced by the heart.
Science
230:
767-770,
1985
12.
Edwards, BS,
Ackermann DM,
Lee ME,
Reeder GS,
Wold LE,
and
Burnett JCJ
Identification of atrial natriuretic factor within ventricular tissue in hamsters and humans with congestive heart failure.
J Clin Invest
81:
82-86,
1988.
13.
Fischer, TA,
Haass M,
Dietz R,
Willenbrock RC,
Saggau W,
Lang RE,
and
Kübler W.
Transcription, storage and release of atrial natriuretic factor in the failing human heart.
Clin Sci
80:
285-291,
1991[Medline].
14.
Flaim, SF,
Minteer WJ,
Nellis SH,
and
Clark DP.
Chronic arteriovenous shunt: evaluation of a model for heart failure in rat.
Am J Physiol Heart Circ Physiol
236:
H698-H704,
1979
15.
Garcia, R,
and
Diebold S.
Simple, rapid, and effective method of producing aortocaval shunts in the rat.
Cardiovasc Res
24:
430-432,
1990
16.
Grantham, JA,
Borgeson DD,
and
Burnett JCJ
BNP: pathophysiological and potential therapeutic roles in acute congestive heart failure.
Am J Physiol Regulatory Integrative Comp Physiol
272:
R1077-R1083,
1997
17.
Gutkowska, J,
Bonan R,
Roy D,
Bourassa M,
Garcia R,
Thibault G,
Genest J,
and
Cantin M.
Atrial natriuretic factor in human plasma.
Biochem Biophys Res Commun
139:
287-295,
1986[Web of Science][Medline].
18.
Hama, N,
Itoh H,
Shirakami G,
Nakagawa O,
Suga S,
Ogawa Y,
Masuda I,
Nakanishi K,
Yoshimasa T,
Hashimoto Y,
Yamaguchi M,
Hori R,
Yasue H,
and
Nakao K.
Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction.
Circulation
92:
1558-1564,
1995
19.
Hanford, DS,
and
Glembotski CC.
Stabilization of the B-type natriuretic peptide mRNA in cardiac myocytes by alpha-adrenergic receptor activation: potential roles for protein kinase C and mitogen-activated protein kinase.
Mol Endocrinol
10:
1719-1727,
1999
20.
Huang, M,
Hester RL,
and
Guyton AC.
Hemodynamic changes in rats after opening an arteriovenous fistula.
Am J Physiol Heart Circ Physiol
262:
H846-H851,
1992
21.
Klinge, R,
Hystad M,
Kjekshus J,
Karlberg BE,
Djoseland O,
Aakvaag A,
and
Hall C.
An experimental study of cardiac natriuretic peptides as markers of development of congestive heart failure.
Scand J Clin Lab Invest
58:
683-691,
1998[Web of Science][Medline].
22.
Kohno, M,
Horio T,
Yokokawa K,
Yasunari K,
Ikeda M,
Minami M,
Kurihara N,
and
Takeda T.
Brain natriuretic peptide as a marker for hypertensive left ventricular hypertrophy: changes during 1-year antihypertensive therapy with angiotensin-converting enzyme inhibitor.
Am J Med
98:
257-265,
1995[Web of Science][Medline].
23.
Lattion, AL,
Michel JB,
Arnauld E,
Corvol P,
and
Soubrier F.
Myocardial recruitment during ANF mRNA increase with volume overload in the rat.
Am J Physiol Heart Circ Physiol
251:
H890-H896,
1986
24.
Luchner, A,
Stevens TL,
Borgeson DD,
Redfield M,
Wei C-M,
Porter JG,
and
Burnett JCJ
Differential atrial and ventricular expression of myocardial BNP during evolution of heart failure.
Am J Physiol Heart Circ Physiol
274:
H1684-H1689,
1998
25.
Magga, J,
Vuolteenaho O,
Tokola H,
Marttila M,
and
Ruskoaho H.
Involvement of transcriptional and posttranscriptional mechanisms in cardiac overload-induced increase of B-type natriuretic peptide gene expression.
Circ Res
81:
694-702,
1997
26.
Mukoyama, M,
Nakao K,
Hosada K,
Suga S,
Saito Y,
Ogawa Y,
Shirakami G,
Jougasaki M,
Obata K,
Yasue H,
Kambayashi Y,
Inouye K,
and
Imura H.
Brain natriuretic peptide as a novel cardiac hormone in humans.
J Clin Invest
87:
1402-1412,
1991.
27.
Nachshon, S,
Zamir O,
Matsuda Y,
and
Zamir N.
Effects of ANP receptor antagonists on ANP secretion from adult rat cultured atrial myocytes.
Am J Physiol Endocrinol Metab
268:
E428-E432,
1995
28.
Nakagawa, O,
Ogawa Y,
Itoh H,
Suga S,
Komatsu Y,
Kishimoto I,
Nishino K,
Yoshimasa T,
and
Nakao K.
Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy.
J Clin Invest
96:
1280-1287,
1995.
29.
Omland, T,
Aakvaag A,
Bonarjee VVS,
Caidahl K,
Lie T,
Nilsen DWT,
Sundsfjord JA,
and
Dickstein K.
Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction.
Circulation
93:
1963-1969,
1996
30.
Perrella, MA,
Schwab TR,
O'Murchu B,
Redfield MM,
Wei CM,
Edwards BS,
and
Burnett JCJ
Cardiac atrial natriuretic factor during evolution of congestive heart failure.
Am J Physiol Heart Circ Physiol
262:
H1248-H1255,
1992
31.
Richards, AM,
Nicholls MG,
Yandle TG,
Frampton C,
Espiner EA,
Turner JG,
Buttimore RC,
Lainchbury JG,
Elliott JM,
Ikram H,
Crozier IG,
and
Smyth DW.
Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin.
Circulation
97:
1921-1929,
1998
32.
Saito, Y,
Nakao K,
Arai H,
Nishimura K,
Okumura K,
Obata K,
Takemura G,
Fujiwara H,
Sugawara A,
Yamada T,
Itoh H,
Mukoyama M,
Hosoda K,
Kawai Ch.,
Ban T,
Yasue H,
and
Imura H.
Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart.
J Clin Invest
83:
298-305,
1989.
33.
Sudoh, T,
Kangawa K,
Minamino N,
and
Matsuo H.
A new natriuretic peptide in porcine brain.
Nature
332:
78-81,
1988[Medline].
34.
Sudoh, T,
Minamino N,
Kangawa K,
and
Matsuo H.
C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain.
Biochem Biophys Res Commun
168:
863-870,
1990[Web of Science][Medline].
35.
Suga, S,
Nakao K,
Itoh H,
Komatsu Y,
Ogawa Y,
Hama N,
and
Imura H.
Endothelial production of C-type natriuretic peptide and its marked augmentation by transforming growth factor-
.
J Clin Invest
90:
1145-1149,
1992.
36.
Takahashi, T,
Allen PD,
and
Izumo S.
Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles.
Circ Res
71:
9-17,
1992
37.
Tsutamoto, T,
Bito K,
and
Kinoshita M.
Plasma atrial natriuretic polypeptides as an index of left ventricular end-diastolic pressure in patients with chronic left-sided heart failure.
Am Heart J
117:
599-606,
1989[Web of Science][Medline].
38.
Vollmar, AM,
Gerbes AL,
Nemer M,
and
Schulz R.
Detection of C-type natriuretic peptide (CNP) transcript in the rat heart and immune organs.
Endocrinology
132:
1872-1874,
1993
39.
Wei, CM,
Heublein DM,
Perrella MA,
Lerman A,
Rodeheffer RJ,
McGregor CGA,
Edwards WD,
Schaff HV,
and
Burnett JCJ
Natriuretic peptide system in human heart failure.
Circulation
88:
1004-1009,
1993
40.
Willenbrock, R,
Haass M,
Osterziel KJ,
Fischer T,
and
Dietz R.
Induktion der atrialen und ventrikulären ANF-Synthese bei experimenteller Herzinsuffizienz nach aortokavalem Shunt.
Z Kardiol
82:
648-653,
1993[Web of Science][Medline].
41.
Yamamoto, K,
Burnett JCJ,
Jougasaki M,
Nishimura RA,
Bailey KR,
Saito Y,
Nakao K,
and
Redfield MM.
Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy.
Hypertension
28:
988-994,
1996
42.
Yasue, H,
Yoshimura M,
Sumida H,
Kikuta K,
Kugiyama K,
Jougasaki M,
Ogawa H,
Okumura K,
Mukoyama M,
and
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
90:
195-203,
1994
43.
Yoshimura, M,
Yasue H,
Okumura K,
Ogawa H,
Jougasaki M,
Mukoyama M,
Nakao K,
and
Imura H.
Different secretion patterns of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart failure.
Circulation
87:
464-469,
1993
44.
Zhong, H,
and
Simons JW.
Direct comparison of GAPDH, beta-actin, cyclophyllin, and 28S rRNA as internal standards for quantifiying RNA levels under hypoxia.
Biochem Biophys Res Commun
259:
523-526,
1999[Web of Science][Medline].
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