Atrial natriuretic factor: a hormone produced by the heart

Systematic studies on the significance of the secretory-like morphological characteristic of cardiac atrial muscle cells of mammals led to the finding that these cells produce a polypeptide hormone. This hormone, described in 1981 as atrial natriuretic factor (ANF), is diuretic (natriuretic), hypotensive, and has an inhibitory effect on renin and aldosterone secretion. Thus, ANF probably intervenes in the short- and long-term control of water and electrolyte balance and of blood pressure. Phylogenetically, ANF appears early, suggesting different functions for this peptide in accordance with each species' environment. Knowledge of the properties of the hormone should provide insights into the pathophysiology of important clinical entities and lead to the development of new pharmaceutical products.     

Inhibition of vasopressin action by atrial natriuretic factor

Atrial natriuretic factor results in diuresis in animals and humans, perhaps because atrial natriuretic factor increases renal blood flow. The possibility that this diuresis is due to direct inhibition of renal tubular epithelial water transport was examined in rabbit collecting tubules perfused in vitro. Atriopeptin III inhibition of the hydraulic conductivity response to the hormone arginine vasopressin but not to either 3'5'-cyclic adenosine monophosphate or forskolin was found. These results suggest that atriopeptin III acts proximal to cyclic adenosine monophosphate formation to directly affect vasopressin-stimulated water transport in the mammalian nephron. They also suggest a potential role for inhibition by atrial natriuretic factor of the renal response to arginine vasopressin as a contributor to a diuretic state.     

Cardiac atria of BIO 14.6 hamsters are deficient in natriuretic factor

The hearts of 220-day-old hamsters of the BIO 14.6 strain are deficient in atrial natriuretic factor; saline extracts of atria produce one-third the natriuretic and diuretic effects of extracts of atria from age-matched normal hamsters. BIO 14.6 hamsters are known to develop congestive heart failure with edema when they are about 200 days old, and the venous congestion and edema are preventable by parabiosis with normal hamsters. The humoral mediator, the deficiency of which causes venous congestion and edema in BIO 14.6 hamsters, may be atrial natriuretic factor.     

Biosynthesis and secretion of proatrial natriuretic factor by cultured rat cardiocytes

Rat atrial natriuretic factor (ANF) is translated as a 152-amino acid precursor preproANF. PreproANF is converted to the 126-amino acid proANF, the storage form of ANF in the atria. ANF isolated from the blood is approximately 25 amino acids long. It is demonstrated here that rat cardiocytes in culture store and secrete proANF. Incubation of proANF with serum produced a smaller ANF peptide. PreproANF seems to be processed to proANF in the atria, and proANF appears to be released into the blood, where it is converted by a protease to a smaller peptide.     

Atrial natriuretic peptide elevation in congestive heart failure in the human

A sensitive radioimmunoassay for atrial natriuretic peptide was used to examine the relation between circulating atrial natriuretic peptide and cardiac filling pressure in normal human subjects, in patients with cardiovascular disease and normal cardiac filling pressure, and in patients with cardiovascular disease and elevated cardiac filling pressure with and without congestive heart failure. The present studies establish a normal range for atrial natriuretic peptide in normal human subjects. These studies also establish that elevated cardiac filling pressure is associated with increased circulating concentrations of atrial natriuretic peptide and that congestive heart failure is not characterized by a deficiency in atrial natriuretic peptide, but with its elevation.     

Coronary vasoconstrictor effects of atriopeptin II

Atrial natriuretic peptides lower arterial pressure, cardiac filling pressure, and cardiac output. In isolated, Langendorff-perfused guinea pig hearts, atriopeptin II, the 23-amino acid atrial natriuretic peptide, is also a potent coronary vasoconstrictor. The median effective dose for atriopeptin II in guinea pig hearts is 26 nanomoles, the threshold constrictor dose is 5 nanomoles, and flow nearly ceases at a dose of 100 nanomoles in perfused hearts at constant pressure. Similar concentrations of atriopeptin II also cause coronary vasoconstriction in rat and dog heart preparations. The disulfide bridge is necessary for vasoconstrictor activity; reduction of this bridge abolishes the activity, as it does the other biological activities of atrial natriuretic peptides.     

The structure of rat preproatrial natriuretic factor as defined by a complementary DNA clone

The structure of rat preproatrial natriuretic factor ( preproANF ) was determined by nucleotide sequence analysis of an ANF complementary DNA clone. PreproANF is composed of a hydrophobic leader segment (20 amino acids), a precursor containing one glycosylation site (106 amino acids), and ANF (24 amino acids). Atrial natriuretic factor is located at the carboxyl terminus of the precursor molecule. The human, mouse, and rat genomes each contain a single ANF gene which is highly conserved.     

Physiological role of silent receptors of atrial natriuretic factor

A ring-deleted analog of atrial natriuretic factor--des[Gln18, Ser19, Gly20, Leu21, Gly22] ANF4-23-NH2 (C-ANF4-23)--binds with high affinity to approximately 99% of ANF receptors in the isolated perfused rat kidney. In this preparation, C-ANF4-23 is devoid of detectable renal effects and does not antagonize any of the known renal hemodynamic and natriuretic actions of biologically active ANF1-28. In contrast, both C-ANF4-23 and ANF1-28 increase sodium excretion and decrease blood pressure in intact anesthetized rats. This apparent contradiction is resolved by the finding that the ring-deleted analog markedly increases plasma levels of endogenous immunoreactive ANF in the rat. The results show that the majority of the renal receptors of ANF are biologically silent. This new class of receptors may serve as specific peripheral storage-clearance binding sites, acting as a hormonal buffer system to modulate plasma levels of ANF.     

Nucleotide sequences of the human and mouse atrial natriuretic factor genes

Mouse and human atrial natriuretic factor (ANF) genes have been cloned and their nucleotide sequences determined. Each ANF gene consists of three coding blocks separated by two intervening sequences. The 5' flanking sequences and those encoding proANF are highly conserved between the two species, while the intervening sequences and 3' untranslated regions are not. The conserved sequences 5' of the gene may play an important role in the regulation of ANF gene expression.     

大鼠急性肾功能衰竭时血浆心钠素与血管紧张素系统的关系

用顺铂（ＣＰ）诱发的大鼠急性肾功能衰竭（ＡＲＦ）动物实验模型，观察在急性肾功能衰竭发展的不同阶段血浆心钠素与肾素、血管紧张素系统之间的关系。发现在ＣＰ处置后２４、４８和７２ｈ，血清肌酐水平分别为正常对照组的１．５、２．５和４倍，同时血浆心钠素水平升高到１．８、２．７和３．６倍。而血浆肾素、血管紧张素系统的活性则相反，血浆肾素在２４ｈ末为正常对照组的２．５倍降低到４８ｈ的１．６倍，并于ＣＰ处置后７２ｈ恢复到正常对照组水平。血管紧张素在２４ｈ末为正常对照组４倍，在４８ｈ末下降４１％，７２ｈ末下降５８％，这表明在急性肾功能衰竭发展过程中，体内分泌的心钠素可能是通过拮抗肾素、血管紧张素系统从而起到肾功能保护的作用。     

人类3个多肽基因的人工合成和对人工基因合成意义的探讨

本文报道了胰岛素A,B链基因,人表皮生长因子基因和人α心钠素基因的人工合成。人工合成是在DNA合成仪上完成的,先合成上述基因的平均为60个核苷酸的各寡核苷酸片段,经过对各片段的纯化、磷酸化和连接,得到上述多肽基因。并进行了电泳检测。人工基因合成的重要意义在于可以正确地、高效地合成基因工程所需的基因,是获得在原核生物中表达的多肽基因的主要途径,并可将重组DNA和表达所需的碱基顺序同时组合在合成的基因中。人工基因合成有广泛的应用前途和价值。     

Alignment of rat cardionatrin sequences with the preprocardionatrin sequence from complementary DNA

Mammalian atria contain peptides that promote the excretion of salt and water from the kidney. When rat atrial tissue is extracted under conditions known to inhibit proteolysis, four natriuretic peptides, cardionatrins I to IV, are consistently isolated. These peptides derive from a common precursor, preprocardionatrin, of 152 amino acids, whose sequence was determined by DNA sequencing of a complementary DNA clone. Amino acid sequencing located the start points of cardionatrins I, III, and IV in the overall sequence. Cardionatrin IV most closely resembles procardionatrin because it begins immediately after the signal sequence at residue 25. Cardionatrin III begins at residue 73, and cardionatrin I, sequenced previously, begins at residue 123. Compositional analysis indicated that each of these cardionatrins extends up to tyrosine at position 150 but lacks the terminal two arginine residues.     

脑钠肽生物学特性及其在心血管病中的应用

脑钠肽（BNP）主要是由心脏分泌和存储的一种神经内分泌激素,为32个氨基酸组成的多肽片段,具有抑制肾素-血管紧张素-醛固酮系统（RAAS）和交感神经系统（SNS）等功能,BNP水平的检测已逐渐被应用于临床,在诊断心力衰竭、心源性哮喘与支气管哮喘的鉴别、评估急性心肌梗死范围等方面具有较大的应用价值,现已成为广大学者关注的焦点.     

Corrections and clarifications

In figure ID (p. 680) of the report "Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension" by Simon W. M. John et al. (3 Feb., p. 679), the size bars to the right and left of the Southern blot were not correctly aligned in relation to the dark bands.     

Atrial natriuretic peptide inhibits a cation channel in renal inner medullary collecting duct cells

The patch-clamp technique was used to examine the effects of atrial natriuretic peptide (ANP) and its second messenger guanosine 3',5'-monophosphate (cGMP) on an amiloride-sensitive cation channel in the apical membrane of renal inner medullary collecting duct cells. Both ANP (10(-11) M) and dibutyryl guanosine 3',5'-monophosphate (10(-4) M) inhibited the channel in cell-attached patches, and cGMP (10(-5) M) inhibited the channel in inside-out patches. The inner medullary collecting duct is the first tissue in which ANP, via its second messenger cGMP, has been shown to regulate single ion channels. The results suggest that the natriuretic action of ANP is related in part to cGMP-mediated inhibition of electrogenic Na+ absorption by the inner medullary collecting duct.     

Angiotensin II- and angiotensin 3-induced aldosterone release vivo in the rat

The potential role of angiotensin II and its heptapeptide metabolite, des-aspartyl-angiotensin II, was studied in the conscious unanesthetized rat. Aldosterone release was induced by both peptides at physiologic doses (0.72 nanogram per minute). [I-Sarcosyl-8-alanyl]-angiotensin II (P-113 inhibited angiotensin II more effectively than des-aspartyl-angiotensin II (101 percent as compared to 82 percent). These results indicate that angiotensin controls aldosterone release in the rat and that des-aspartyl-angiotensin II (that is, angiotensin III) may be important in this sequence.     

鼠急性肾功能衰竭时血浆心钠素动态变化及其与肾功能的关系

用顺铂（ＣＰ）复制大鼠急性肾功能衰竭动物模型，动态观察急性肾功能衰竭各阶段的血浆心钠素（ＰＡＮＰ）变化及其与肾功能的关系。在采用ＣＰ处理后２４ｈ和７２ｈ，血清肌酐分别升高为正常对照组的１．５和４倍，同时血浆心钠素水平升高到１．８和３．６倍。血浆ｃＧＭＰ水平也与血浆心钠素水平一道平行升高。这表明血浆心钠素水平的变化与肾功能损害程度密切相关。     

Coexistence of guanylate cyclase and atrial natriuretic factor receptor in a 180-kD protein

Atrial natriuretic factor (ANF) is a peptide hormone that is released from atria and regulates a number of physiological processes, including steroidogenesis in adrenal cortex and testes. The parallel stimulation of membrane guanylate cyclase and corticosterone production in isolated fasciculata cells of rat adrenal cortex has supported the hypothesis of a mediatory role for cyclic guanosine monophosphate (cyclic GMP) in signal transduction. A novel particulate guanylate cyclase tightly coupled with ANF receptor was purified approximately 273,000-fold by two-step affinity chromatography. The enzyme had a molecular size of 180 kilodaltons and was acidic in nature with a pI of 4.7. Its specific activity was 1800 nanomoles of cyclic GMP formed per minute per milligram of protein. The purified enzyme bound ANF with a specific binding activity of 4.01 nanomoles per milligram of protein, a value that is close to the theoretical binding activity of 5.55 nanomoles per milligram of protein for 1 mole of the ligand binding 1 mole of the receptor protein. These results indicate that the guanylate cyclase-coupled ANF receptor exists in a 180-kilodalton protein of rat adrenocortical carcinoma and represent a step toward the elucidation of the basic mechanism of cyclic GMP-mediated transmembrane signal transduction in response to a hormone.     

Ser-Leu-Arg-Arg-atriopeptin III: the major circulating form of atrial peptide

Vasopressin induces a concentration-dependent increase in atriopeptin immunoreactivity in plasma. Rat plasma, rat atrial extract, and synthetic atriopeptin III (APIII) produced parallel displacement curves of iodine-125-labeled APIII binding to specific antiserum. Fractionation of plasma atriopeptin immunoreactivity by reverse-phase high-performance liquid chromatography showed that the major portion consists of two species of low molecular weight peptides in a ratio of 10 to 1. Both peaks exhibited potent vasorelaxant activity, suggesting the presence of the carboxyl terminal Phe-Arg sequence of atriopeptin in each species. Sequence determination of the purified peptides indicated that the major peptide is Ser-Leu-Arg-Arg-APIII and the minor peptide APIII. It appears that the former is the major species of atrial peptide in the rat circulation and that it is the product of selective cleavage of the high molecular weight precursor.     

Control of aldosterone secretion by the pituitary gland

In the rat, the pituitary gland is essential for the stimulation of aldosterone secretion by sodium depletion. Hypophysectomy abolishes the response to sodium depletion, whereas whole pituitary gland injections partially restore it. The response cannot be restored by injections of either adrenocorticotropin or growth hormone, nor by adrenocorticotropin plus thyroxin. The pituitary gland must secrete a hormone or possibly several hormones which are necessary for the adrenal gland to respond to sodium depletion.