Identification of a biologically active circulating form of rat atrial natriuretic factor

Thibault, Gaétan; Lazure, Claude; Schiffrin, Ernesto L.; Gutkowska, Jolanta; Chartier, Lynn; García, Raúl; Seidah, Nabil G.; Chrétien, Michel; Genest, Jacques; Cantin, M.

doi:10.1016/0006-291x(85)91711-5

Cited by 159 publications

(35 citation statements)

References 16 publications

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“…At the time these studies were initiated, the exact sequence of the circulating form(s) of ANF was uncertain, and a synthetic 25-residue peptide (mol wt 2,508), based on the sequence of rat auriculin B (16) and corresponding to amino acids 102-126 of the ANF precursor, was studied. Recently it has been shown that a 28-residue peptide (mol wt 3,100), termed cardionatrin I (17) or ANF 99-126, is the principal form of ANF in rat blood (18,19). The peptide used in these studies corresponds to residues 4-28 of the latter peptide and differs from the corresponding human sequence by a single amino acid substitution (Ile for Met at position 12); however, the 25-and 28-residue peptides have very similar biological potency both in vitro and in vivo (5).…”

Section: Glossarymentioning

confidence: 99%

Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

Cody¹,

Atlas²,

Laragh³

et al. 1986

J. Clin. Invest.

685

180

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We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11±0.9 fmol/ml in NL and 71±9.9 in CHF (P < 0.01); the latter with twofold night ventricular increment (P < 0.05). In NL, ANF infusion of 0.10 ig/ kg per min (40 pmol/kg per min) induced increases (P < 0.05) of absolute (from 160±23 to 725±198 iseq/min) and fractional(1-4%) sodium excretion, urine flow rate (from 10±1.6 to 20±2.6 ml/min), osmolar (from 3.2±0.6 to 6.8±1.2 ml/min) and free water (from 6.8±1.6 to 13.6±1.6 ml/min) clearances, and filtration fraction (from 20±1 to 26±2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P < 0.01). Systolic blood pressure fell (from 112±3 to 104±5 mmHg, P < 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11±1 to 7±1 mmHg, P < 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P < 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P < 0.05) but not in CHF.

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Section: Glossarymentioning

confidence: 99%

Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

Cody¹,

Atlas²,

Laragh³

et al. 1986

J. Clin. Invest.

685

180

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“…Antibodies were raised in New Zealand white rabbits immunized with synthetic a-hANP [17-28] (35). This RIA recognizes the C-terminal portion of a-hANP and detects a-hANP and a-hANP [17][18][19][20][21][22][23][24][25][26][27][28] equally on a molar basis (35).…”

Section: Radioimmunoassay For Anpmentioning

confidence: 99%

“…Fragments of ANP such as a-hANP [1][2][3][4][5][6], a-hANP [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and a-hANP [24][25][26][27][28] were donated by Dr. Y. Kiso (Kyoto Pharmaceutical University, Kyoto, Japan) (38).…”

Section: Radioimmunoassay For Anpmentioning

confidence: 99%

“…Several lines of studies including ours using high performance gel permeation chromatography (HP-GPC) and reverse phase high performance liquid chromatography (RP-HPLC) coupled with RIA for ANP revealed that ANP is stored in secretory granules of atrial cardiocytes as the 126-amino acid precursor, y-ANP, and only a little amount of a-ANP was detectable in the atrium, especially in animals (4,5,(14)(15)(16). It has also been reported that the secretory and circulating form of ANP is a small molecular weight form of 28-amino acid peptide, a-ANP (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Thus, the heart is now regarded as an endocrine organ secreting ANP as well as a pump organ, and the relationship between endocrine and hemodynamic functions of the heart attracts interests of many investigators (10,11,(26)(27)(28)(29)(30)(31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of atrial natriuretic polypeptide in human failing hearts. Evidence for altered processing of atrial natriuretic polypeptide precursor and augmented synthesis of beta-human ANP.

Sugawara¹,

Nakao²,

Morii³

et al. 1988

J. Clin. Invest.

101

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To elucidate the synthesis of atrial natriuretic polypeptide (ANP) in the failing heart, 20 human right auricles obtained at cardiovascular surgery were studied. The concentration of ahuman ANP-like immunoreactivity (a-hANP-LI) in human right auricles ranged from 13.8 to 593.5 Ag/g, and the tissue a-hANP-LI concentration in severe congestive heart failure (CHF) (New York Heart Association [NYHAI functional class III and class IV) (235.4±57.2 gg/g) was much higher than that in mild CHF (NYHA class I and class II) (52. 5±15.6 Ag/g). Atrial a-hANP-LI levels were significantly correlated with plasma concentrations of a-hANP-LI in these patients (r = 0.84, P < 0.01).High performance gel permeation chromatography and reverse phase high performance liquid chromatography coupled with radioimmunoassay for ANP revealed that the a-hANP-LI in the human auricle consisted of three major components of ANP, v-human ANP ('y-hANP), 6%human ANP (8-hANP) and a-human ANP (a-hANP). Comparing percentages of 'yhANP, fl-hANP, and a-hANP in a-hANP-LI in severe CHF with those in mild CHF, the predominant component of ahANP-LI was y-hANP in mild CHF, whereas 8-hANP and/or a-hANP were prevailing in severe CHF and, especially, 8-hANP was markedly increased in human failing hearts.These results demonstrate that the total ANP concentration in the atrium of the human heart is increased in severe CHF and that the increase of ANP in the human failing heart is mainly due to the increase of small molecular weight forms of ANP,,j-hANP, and a-hANP, especially ,8-hANP, and indicate that the processing of ANP precursor, or 'y-hANP, in the human failing heart differs from that in the normal heart, suggesting that the failing heart augments synthesis and secretion of ANP as one of its own compensatory responses.

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“…It is processed to low-molecularweight ANP during exocytosis (33), presumably by the membrane-bound serine protease corin (36). The products are the 28-amino-acid biologically active ANP and the inert 98-amino-acid NH 2 -terminal fragment NTproANP (8,31). The elimination of ANP from the circulation is very rapid, resulting in low and labile plasma concentrations.…”

mentioning

confidence: 99%

Pronatriuretic peptide is a sensitive marker of the endocrine function of teleost heart

Vierimaa¹,

Hirvinen²,

Tervonen³

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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We recently characterized a novel heart-specific hormone from salmon (salmon cardiac peptide, sCP). We have now prepared a recombinant plasmid expressing the NH2-terminal fragment of pro-sCP (NT-pro-sCP) and used it to set up a specific RIA for the peptide. Because of the sensitivity of the assay and the high circulating levels, NTpro-sCP can be measured from as little as 2 l of serum. This enables repeated sampling from the same animal in different experimental setups. Mechanical load increased the release of NT-pro-sCP from isolated perfused salmon ventricle, in parallel with sCP. Bolus injection of human endothelin-1 (ET-1; 1 g) in the dorsal aorta of salmon resulted in an extensive increase of serum NT-pro-sCP (from 0.99 Ϯ 0.11 to 4.6 Ϯ 1.5 nmol/l). The response was abolished by pretreatment with a specific type A ET (ETA) receptor antagonist (BQ-123) but not with a type B ET receptor antagonist (BQ-788).The NT-pro-sCP levels had a good correlation with those of sCP (r 2 ϭ 0.75). Our results demonstrate the practical usefulness of circulating NT-pro-sCP as a marker of the endocrine function of salmon heart. They also suggest that ET-1 has an important role in regulating sCP release from teleost heart by an ETA receptor-mediated mechanism. natriuretic peptide; endothelin; recombinant protein; radioimmunoassay; study in vivo NATRIURETIC PEPTIDES are cardiac hormones with an important role in regulating cardiovascular and fluid homeostasis (2). The release of A-and B-type natriuretic peptides (ANP and BNP) from the heart is stimulated by increased load (11,14,18) and by various paracrine factors, such as endothelin-1 (3, 16, 30). They reduce the cardiac load by causing natriuresis, diuresis, and relaxation of the vascular smooth muscle and by inhibiting the renin-angiotensin-aldosterone system (21). Although blood volume expansion is an important stimulus for ANP secretion in mammals, in nonmammalian eel, ANP secretion has been reported to be more sensitive to osmotic than volemic stimuli. In this teleost, ANP causes excretion of Na ϩ , thereby promoting adaptation to seawater (9).In mammals, ANP is stored in the secretory granules of atrial myocytes as a large-molecular-weight prohormone (proANP). It is processed to low-molecularweight ANP during exocytosis (33), presumably by the membrane-bound serine protease corin (36). The products are the 28-amino-acid biologically active ANP and the inert 98-amino-acid NH 2 -terminal fragment NTproANP (8,31). The elimination of ANP from the circulation is very rapid, resulting in low and labile plasma concentrations. The half-life of rat NT-proANP in rat circulation has been reported to be eight times longer than that of ANP (32). Therefore, and because its plasma concentrations are much higher, the measurement of NT-proANP is preferred over that of ANP in the assessment of cardiac function, e.g., in patients with congestive heart failure (22). The same appears to apply for .We have recently cloned and characterized from salmon a novel peptide hormone, salmon cardiac pep...

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Identification of a biologically active circulating form of rat atrial natriuretic factor

Cited by 159 publications

References 16 publications

Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

Synthesis of atrial natriuretic polypeptide in human failing hearts. Evidence for altered processing of atrial natriuretic polypeptide precursor and augmented synthesis of beta-human ANP.

Pronatriuretic peptide is a sensitive marker of the endocrine function of teleost heart

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