Pulsatile secretion of atrial natriuretic peptide and brain natriuretic peptide in healthy humans

Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are involved in sodium and water homoeostasis in healthy humans. The plasma concentrations of the natriuretic peptides can be used to differentiate between dyspnoea of cardiac and pulmonary origin, and the degree of elevation of the peptide levels in the plasma in heart failure is a measure of the severity of the disease. However, the patterns of secretion of ANP and BNP are not clear either in healthy humans or in patients. The purpose of the present study was to test the hypotheses that both ANP and BNP are secreted in pulses in healthy humans, and that this phenomenon can be revealed by determination of ANP and BNP in peripheral venous blood samples. In 12 healthy subjects, blood samples were drawn every 2 min through an intravenously inserted plastic needle over a period of 2 h. Plasma concentrations of ANP and BNP were determined by RIAs, and the results were analysed for pulsatile behaviour by Fourier transformation. Pulsatile secretion of ANP was seen in 10 out of 12 subjects [ν = 0.028 min-1 (median; range 0.013–0.047 min-1), i.e. a pulse of ANP with an interval of 36 min (range 21–77 min)]. Pulsatile secretion of BNP was seen in nine out of 12 patients [ν = 0.021 min-1 (range 0.013–0.042 min-1), i.e. a pulse of BNP with an interval of 48 min (range 24–77 min)]. The main conclusion is that the secretion patterns of both ANP and BNP are pulsatile in most healthy humans. Consequently, it is important to study whether pulsatile secretion also occurs in heart failure in order to obtain the most informative predictive values both in the differential diagnosis of dyspnoea and in the evaluation of the severity of the disease.

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Abnormal rhythmic oscillations of atrial natriuretic peptide and brain natriuretic peptide in heart failure

Clinical Science ◽

10.1042/cs1040303 ◽

2003 ◽

Vol 104 (3) ◽

pp. 303-312 ◽

Cited By ~ 10

Author(s):

Hans BENTZEN ◽

Robert S. PEDERSEN ◽

Henrik B. PEDERSEN ◽

Ole NYVAD ◽

Erling B. PEDERSEN

Keyword(s):

Heart Failure ◽

Atrial Natriuretic Peptide ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Left Ventricular ◽

Control Group ◽

Pulsatile Secretion ◽

Main Frequency ◽

Healthy Humans ◽

Atrial Natriuretic

The purpose of this study was to clarify whether the secretions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are pulsatile in patients with chronic heart failure (CHF), and whether the rhythmic oscillations for ANP and BNP are abnormal in patients with CHF. Several reports have shown that ANP and especially BNP are valuable indicators of the prognosis in CHF. Previously, a pulsatile secretion has been described for ANP and BNP in healthy humans and for ANP in CHF patients. More information about the secretion pattern of BNP in heart failure is necessary to increase the clinical usefulness of BNP in patients with CHF. Patients with left ventricular systolic dysfunction and CHF (n = 12) and controls (n = 12) were investigated. Plasma ANP and BNP levels were determined every 2min during a 2-h period by radioimmunoassay and analysed for pulsatile behaviour by Fourier transformation. All patients and controls had significant rhythmic oscillations in plasma ANP levels, and 11 patients with CHF and 10 controls had significant rhythmic oscillations in plasma BNP levels. The amplitude of the main frequency was considerably higher in patients with CHF than in controls (ANP: CHF, 4.76pmol/l; controls, 0.75pmol/l; P<0.01. BNP: CHF, 3.24pmol/l; controls, 0.23pmol/l; P<0.001; all values are medians), but the main frequency did not differ significantly between the group with CHF and the control group for either ANP or BNP. Patients with CHF demonstrate pulsatile secretion of ANP and BNP with a much higher absolute amplitude, but with the same main frequency as healthy subjects.

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Biological effects of rat iso-atrial natriuretic peptide and brain natriuretic peptide are indistinguishable from each other

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-218 ◽

1992 ◽

Vol 70 (11) ◽

pp. 1525-1528 ◽

Cited By ~ 6

Author(s):

D. A. Wigle ◽

B. M. Bennett ◽

D. B. Jennings ◽

I. R. Sarda ◽

T. G. Flynn ◽

...

Keyword(s):

Amino Acid ◽

Atrial Natriuretic Peptide ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Receptor Binding ◽

Amino Acid Substitution ◽

Cyclic Gmp ◽

Cardiovascular Response ◽

Biological Effects ◽

Atrial Natriuretic

Rat brain natriuretic peptide (rBNP) and iso-atrial natriuretic peptide (iso-rANP) were discovered independently by two research laboratories. They are considered to be members of the B-type natriuretic peptides. Except for the Gln/Leu substitution at position 44, the amino acid sequence of iso-rANP is identical with that of the C-terminal 45 amino acids of rat pro-BNP and with the 5-kDa cardiac peptide from rat atria. To determine whether this amino acid substitution can modify the known biological effects of rBNP and iso-rANP, the present investigation examined the cardiovascular and renal responses, vasorelaxant effect, receptor binding characteristics, and cyclic GMP production by the two peptides in relation to that of rat atrial natriuretic peptide (rANP). Results indicate that rBNP and iso-rANP are indistinguishable from each other in terms of these known biological activities of atrial natriuretic peptide. We therefore conclude that rBNP and iso-rANP are identical peptides and that the amino acid substitution at position 44 represents a polymorphic form of the rat B-type natriuretic peptide.Key words: atrial natriuretic peptide, brain natriuretic peptide, cardiovascular response, vasorelaxation, cyclic GMP, receptor binding.

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Alteration of Atrial Natriuretic Peptide and Brain Natriuretic Peptide Gene Expression Associated with Progression and Regression of Cardiac Hypertrophy in Renovascular Hypertensive Rats

Clinical Science ◽

10.1042/cs0900197 ◽

1996 ◽

Vol 90 (3) ◽

pp. 197-204 ◽

Cited By ~ 20

Author(s):

Hideo Kawakami ◽

Hideki Okayama ◽

Mareomi Hamada ◽

Kunio Hiwada

Keyword(s):

Gene Expression ◽

Atrial Natriuretic Peptide ◽

Cardiac Hypertrophy ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Mrna Levels ◽

Hypertensive Rats ◽

Regression Of Cardiac Hypertrophy ◽

Peptide Gene ◽

Atrial Natriuretic

1. We assessed the changes of atrial natriuretic peptide and brain natriuretic peptide gene expression associated with progression and regression of cardiac hypertrophy in renovascular hypertensive rats (RHR). 2. Two-kidney, one-clip hypertensive rats (6-week-old male Wistar) were made and studied 6 (RHR-1) and 10 weeks (RHR-2) after the procedure. Regression of cardiac hypertrophy was induced by nephrectomy at 6 weeks after constriction, and the nephrectomized rats were maintained further for 4 weeks (nephrectomized rat: NEP). Sham operation was performed, and the rats were studied after 6 (Sham-1) and 10 weeks (Sham-2). Atrial natriuretic peptide and brain natriuretic peptide gene expression in the left ventricle was analysed by Northern blotting. 3. Plasma atrial natriuretic peptide and brain natriuretic peptide were significantly higher in RHR-1 and RHR-2 than in Sham-1, Sham-2 and NEP. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in RHR-1 were approximately 7.2-fold and 1.8-fold higher than those in Sham-1, respectively, and the corresponding levels in RHR-2 were 13.0-fold and 2.4-fold higher than those in Sham-2, respectively. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels of NEP were normalized. Levels of atrial natriuretic peptide and brain natriuretic peptide mRNA were well correlated positively with left ventricular weight/body weight ratios. There was a significant positive correlation between the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA (r = 0.86, P<0.01). 4. We conclude that the expression of atrial natriuretic peptide and brain natriuretic peptide genes is regulated in accordance with the degree of myocardial hypertrophy and that the augmented expression of these two natriuretic peptides may play an important role in the maintenance of cardiovascular haemodynamics in renovascular hypertension.

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Evaluation of Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Atrial Granules of Rats with Experimental Congestive Heart Failure

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215540104901012 ◽

2001 ◽

Vol 49 (10) ◽

pp. 1293-1300 ◽

Cited By ~ 16

Author(s):

Gad M. Bialik ◽

Zaid A. Abassi ◽

Ilan Hammel ◽

Joseph Winaver ◽

Dina Lewinson

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Atrial Natriuretic Peptide ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Aortocaval Fistula ◽

Granule Formation ◽

Gold Particles ◽

The Mean ◽

Atrial Natriuretic

The natriuretic peptides are believed to play an important role in the pathophysiology of congestive heart failure (CHF). We utilized a quantitative cytomorphometric method, using double immunocytochemical labeling, to assess the characteristics of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in atrial granules in an experimental model of rats with CHF induced by aortocaval fistula. Rats with CHF were further divided into decompensated (sodium-retaining) and compensated (sodium-excreting) subgroups and compared with a sham-operated control group. A total of 947 granules in myocytes in the right atrium were analyzed, using electron microscopy and a computerized analysis system. Decompensated CHF was associated with alterations in the modal nature of granule content packing, as depicted by moving bin analysis, and in the granule density of both peptides. In control rats, the mean density of gold particles attached to both peptides was 347.0 ± 103.6 and 306.3 ± 89.9 gold particles/μm2 for ANP and BNP, respectively. Similar mean density was revealed in the compensated rats (390.6 ± 81.0 and 351.3 ± 62.1 gold particles/μm2 for ANP and BNP, respectively). However, in rats with decompensated CHF, a significant decrease in the mean density of gold particles was observed (141.6 ± 67.3 and 158.0 ± 71.2 gold particles/μm2 for ANP and BNP, respectively; p < 0.05 compared with compensated rats, for both ANP and BNP). The ANP:BNP ratio did not differ between groups. These findings indicate that the development of decompensated CHF in rats with aortocaval fistula is associated with a marked decrease in the density of both peptides in atrial granules, as well as in alterations in the quantal nature of granule formation. The data further suggest that both peptides, ANP and BNP, may be regulated in the atrium by a common secretory mechanism in CHF.

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Effect of endopeptidase-24.11 inhibition and of atrial natriuretic peptide clearance receptor ligand on the response to rat brain natriuretic peptide in the conscious rat

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1993.tb13816.x ◽

1993 ◽

Vol 110 (1) ◽

pp. 350-354 ◽

Cited By ~ 6

Author(s):

Jane E. Kirk ◽

M.R. Wilkins

Keyword(s):

Atrial Natriuretic Peptide ◽

Brain Natriuretic Peptide ◽

Rat Brain ◽

Natriuretic Peptide ◽

Conscious Rat ◽

Receptor Ligand ◽

Endopeptidase 24.11 ◽

Clearance Receptor ◽

Atrial Natriuretic

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Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic peptide over atrial natriuretic peptide

Biochemical Journal ◽

10.1042/0264-6021:3580379 ◽

2001 ◽

Vol 358 (2) ◽

pp. 379 ◽

Cited By ~ 9

Author(s):

Michael F. GOY ◽

Paula M. OLIVER ◽

Kit E. PURDY ◽

Joshua W. KNOWLES ◽

Jennifer E. FOX ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Natriuretic Peptide Receptor ◽

Peptide Receptor ◽

Atrial Natriuretic

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Effects of Physiological Increments in Human α-Atrial Natriuretic Peptide and Human Brain Natriuretic Peptide in Normal Male Subjects

Clinical Science ◽

10.1042/cs0860723 ◽

1994 ◽

Vol 86 (6) ◽

pp. 723-730 ◽

Cited By ~ 22

Author(s):

B. M. Y. Cheung ◽

J. E. C. Dickerson ◽

M. J. Ashby ◽

M. J. Brown ◽

J. Brown

Keyword(s):

Atrial Natriuretic Peptide ◽

Human Brain ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Physiological Role ◽

Sodium Balance ◽

Urinary Flow ◽

Male Subjects ◽

The Brain ◽

Atrial Natriuretic

1. Brain natriuretic peptide, closely related to atrial natriuretic peptide in structure, may be an important circulating hormone. Its physiological role is unclear. First, we studied the effects of incremental infusions of brain natriuretic peptide in six healthy men on plasma brain natriuretic peptide levels and the pharmacokinetics of brain natriuretic peptide. Synthetic human brain natriuretic peptide-32 was infused intravenously, at an initial rate of 0.4 pmol min−1 kg−1, doubling every 15 min until the dose rate reached 6.4 pmol min−1 kg−1, at which rate the infusion was maintained for 30 min. 2. The brain natriuretic peptide infusion raised the brain natriuretic peptide-like immunoreactivity from 1.4 ± 0.5 pmol/l to 21.4 ± 7.6 pmol/l. Brain natriuretic peptide-like immunoreactivity after the end of infusion was consistent with a bi-exponential decay, with half-lives of 2.1 min and 37 min. 3. Next, we studied the effects of low-dose infusion of brain natriuretic peptide to mimic physiological increments in the circulating levels in comparison with atrial natriuretic peptide. Six dehydrated male subjects received intravenous infusions of atrial natriuretic peptide and brain natriuretic peptide, separately and in combination, in a randomized double-blind, placebo-controlled, four-part cross-over design. Atrial natriuretic peptide and brain natriuretic peptide were given at the rate of 0.75 and 0.4 pmol min−1 kg−1, respectively, for 3 h. The control infusion consisted of the vehicle. 4. Analysis of variance showed that atrial natriuretic peptide and atrial natriuretic peptide plus brain natriuretic peptide, but not brain natriuretic peptide alone, increased urinary flow and decreased urinary osmolality significantly. However, urinary sodium excretion was significantly increased by atrial natriuretic peptide, brain natriuretic peptide and atrial natriuretic peptide plus brain natriuretic peptide. 5. None of the four infusates significantly altered the blood pressure, heart rate or glomerular filtration rate. 6. This study showed, for the first time, that physiological increments in brain natriuretic peptide, like those in atrial natriuretic peptide, are natriuretic. Although atrial natriuretic peptide and brain natriuretic peptide do not appear to interact synergistically, they are likely to act in concert in the physiological regulation of sodium balance.

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Low-Dose Brain Natriuretic Peptide Infusion in Normal Men and the Influence of Endopeptidase Inhibition

Clinical Science ◽

10.1042/cs0920255 ◽

1997 ◽

Vol 92 (3) ◽

pp. 255-260 ◽

Cited By ~ 13

Author(s):

C. M. Florkowski ◽

A. M. Richards ◽

E. A. Espiner ◽

T. G. Yandle ◽

E. Sybertz ◽

...

Keyword(s):

Atrial Natriuretic Peptide ◽

Plasma Renin Activity ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Low Dose ◽

Plasma Renin ◽

Renin Activity ◽

Plasma Brain Natriuretic Peptide ◽

Normal Men ◽

Atrial Natriuretic

1. To assess the threshold dose for bioactivity of brain natriuretic peptide and the role of endopeptidase 24.11 in metabolism of brain natriuretic peptide at physiological plasma levels, we studied eight normal men receiving 2 h infusions of low-dose brain natriuretic peptide [0.25 and 0.5 pmol min−1 kg−1 with and without pretreatment with an endopeptidase inhibitor (SCH 32615, 250 mg intravenously)] in placebo-controlled studies. 2. Plasma brain natriuretic peptide increased 2-fold during the infusion of 0.25 pmol min−1 kg−1 (mean increment above control 3.9 pmol/l, P < 0.001), and tripled (P < 0.001) with 0.5 pmol min−1 kg−1. Plasma renin activity was inhibited by both doses (14.8%, P < 0.01, and 20%, P < 0.001, respectively). A significant natriuresis (56% increase in urine sodium/creatinine ratio, P < 0.02) occurred with the higher dose. Blood pressure, haematocrit, plasma cGMP, atrial natriuretic peptide and aldosterone were unaffected by either dose. 3. Compared with brain natriuretic peptide (0.5 pmol min−1 kg−1) alone, SCH 32615 pretreatment increased peak plasma brain natriuretic peptide (13.4±0.78 versus 12.4±0.86 pmol/l, P < 0.05), ANP (7.5±0.96 versus 5.9±0.4 pmol/l, P < 0.01) and cGMP (4.8 ± 1.7 versus 3.9 ± 1.4 nmol/l, P < 0.001). Plasma renin activity was further suppressed with SCH 32615 pretreatment (29% compared with 20%, P < 0.001). 4. Small acute increments in plasma brain natriuretic peptide (4 pmol/l) have significant biological effects in normal men without altering plasma atrial natriuretic peptide or cGMP.

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