Neonatal atria and ventricles secrete atrial natriuretic factor via tissue-specific secretory pathways

doi:10.1016/0092-8674(86)90512-X

Cell

Volume 47, Issue 5, 5 December 1986, Pages 695-702

https://doi.org/10.1016/0092-8674(86)90512-X Get rights and content

Abstract

The cellular mechanisms regulating secretion of the peptide hormone atrial natriuretic factor (ANF) differ in neonatal atrial and ventricular cardiocytes. We demonstrate that although both cell types synthesize and secrete ANF, only atrial cells store peptide in abundant secretory granules. Neonatal ventricular cells secrete ANF rapidly after synthesis and lack secretory granules. We propose that ventricular ANF is released by a constitutive secretory pathway whereas atrial ANF is stored and released by a regulated pathway. Furthermore, ventricular ANF mRNA and hormone concentrations decrease during the first week of life. Developmental variation in the use of ANF secretory pathways may reflect changing requirements for maintenance of intravascular volume and pressure. Tissue-specific modulation of hormone secretory pathways appears to be a novel response to developmentally induced changes in the requirements for a peptide hormone.

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Cited by (237)

zDHHC9 Regulates Cardiomyocyte Rab3a Activity and Atrial Natriuretic Peptide Secretion Through Palmitoylation of Rab3gap1
2023, JACC: Basic to Translational Science
Production and release of natriuretic peptides by the stressed heart reduce cardiac workload by promoting vasodilation, natriuresis, and diuresis, which has been leveraged in the recent development of novel heart-failure pharmacotherapies, yet the mechanisms regulating cardiomyocyte exocytosis and natriuretic peptide release remain ill defined. We found that the Golgi S-acyltransferase zDHHC9 palmitoylates Rab3gap1 resulting in its spatial segregation from Rab3a, elevation of Rab3a-GTP levels, formation of Rab3a-positive peripheral vesicles, and impairment of exocytosis that limits atrial natriuretic peptide release. This novel pathway potentially can be exploited for targeting natriuretic peptide signaling in the treatment of heart failure.
The expression of natriuretic peptide receptors in developing zebrafish embryos
2018, Gene Expression Patterns
There are three isoforms of natriuretic peptide (NP) specific cell surface receptor: NP receptor-A (NPRA), receptor-B (NPRB), and receptor-C (NPRC). They are also known as NPR1, NPR2 and NPR3, respectively. NPs and their receptors were revealed to involve in diverse cellular and physiological processes including renal, cardiovascular, neuronal, and immunological aspects. However, the systematic analysis of the expression of these receptors in non-mammalian vertebrates is thus far lacking. In this study, two versions of the npr1 gene (npr1a and npr1b) in zebrafish was identified. Multiple sequences alignment analysis showed that zebrafish NPRs shared high homologies with NPRs of other species and possessed a typical signature domain of NPRs. The results of whole mount in situ hybridization and reverse transcription polymerase chain reaction analysis revealed that at embryonic stages, npr1a was mainly expressed in tectal ventricle, brian, heart and retina, whereas npr1b was broadly present in anterior pronephric duct. Unlike npr1, npr2 mainly expressed in branchial arches and neural tube during embryonic development. However, npr3 was expressed in pronephric ducts and corpuscle of stannius in zebrafish embryos at 72 hpf. In adults, we demonstrated that all the three NP receptors were highly existed in brain and kidney. Overall, these findings will provide an important basis for the functional analysis of NPs and its receptor during embryonic development.
Differential expression and regulation of anti-hypertrophic genes Npr1 and Npr2 during β-adrenergic receptor activation-induced hypertrophic growth in rats
2016, Molecular and Cellular Endocrinology
Citation Excerpt :
Our results are in agreement with the reports of Yoshimoto T et al., supporting the notion that an interaction between the β-AR signaling axis and ANP/NPR-A system in the heart could be the reason for the altered circulatory levels of ANP and CNP in the ISO induced hypertrophied rats (Yoshimoto et al., 1998). The ANP gene expression is absent or even undetectable in the adult ventricles (Bloch et al., 1986). However, several reports have demonstrated that the ventricle is capable of synthesizing and storing substantial amounts of ANP during cardiac hypertrophy and heart failure conditions (Thibault et al., 1989).
We sought to determine the effect of chronic activation of β-adrenergic receptor (β-AR) on the left ventricular (LV) expression profile of Npr1 and Npr2 (coding for NPR-A and NPR-B, respectively) genes, and the functional activity of these receptors in adult Wistar rat hearts. The Npr1 gene expression was markedly reduced (3.5-fold), while the Npr2 gene expression was up regulated (4-fold) in Isoproterenol (ISO)-treated heart as compared with controls. A gradual reduction in NPR-A protein (3-fold), cGMP levels (75%) and a steady increased expression of NPR-B protein (4-fold), were noticed in ISO hearts. Further, in-vitro membranes assay shows that NPR-A dependent guanylyl cyclase (GC) activity was down-regulated (2-fold), whereas NPR-B dependent GC activity was increased (5-fold) in ISO treated hearts. Atenolol treatment normalized the altered expression of Npr1 and Npr2 genes. In conclusion, the chronic β-AR activation differentially regulates Npr1 and Npr2 genes in the heart. Npr1 down regulation is positively associated with the development of left ventricular hypertrophy (LVH) in ISO rats.
Oleanolic acid increases plasma ANP levels via an accentuation of cardiac ANP synthesis and secretion in rats
2013, European Journal of Pharmacology
Oleanolic acid is known to have beneficial effects on the regulation of cardiovascular homeostasis. The present study was designed to identify the effects of oleanolic acid on plasma levels and atrial synthesis and secretion of atrial natriuretic peptide (ANP). Experiments were performed in rats and isolated perfused beating rat atria. ANP was measured using a selective radioimmunoassay. ANP mRNA expression was measured using real-time quantitative polymerase chain reaction. Administration of oleanolic acid increased plasma ANP levels in a dose-related manner. Similarly, oleanolic acid increased atrial ANP content and ANP mRNA expression. To evaluate the effects of oleanolic acid on ANP secretion, atrial stretch and muscarinic acetylcholine receptor activation were applied to the atria from rats chronically treated with oleanolic acid. Baseline levels of ANP secretion were higher in the atria from rats treated with oleanolic acid compared to rats treated with vehicle. Furthermore, oleanolic acid treatment enhanced the stretch-induced increase in ANP secretion. Acetylcholine in the presence of isoproterenol increased ANP secretion. The acetylcholine-induced increase in ANP secretion was also enhanced in the atria from rats treated with oleanolic acid compared to atria from rats treated with vehicle. The present findings indicate that oleanolic acid increases plasma ANP levels via increased ANP synthesis and secretion in rats. It is proposed that an accentuation of the ANP system is involved in the beneficial effects of oleanolic acid on the regulation of cardiovascular homeostasis.
SNARE protein regulation of cardiac potassium channels and atrial natriuretic factor secretion
2011, Journal of Molecular and Cellular Cardiology
Citation Excerpt :
This led to the discovery and cloning of ANF, BNP and CNP [63]. ANF secretion was then found to be elicited primarily by atrial stretch [59]; however, hormonal (endothelin-1) and α1-adrenergic stimulation also stimulate ANF release [61]. Hypertension, congestive heart and renal failure, and diabetes are associated with elevated plasma ANF levels [61].
Coordinated cardiac ion channel gating is fundamental for generation of action potential and excitability throughout the myocardium. The interaction of pore-forming ion channels with auxiliary subunits can regulate surface expression, localization and anchoring of these channels to plasma membrane. SNARE (soluble N-ethylmaleimide sensitive factors attachment protein or SNAP receptor) proteins mediate the targeting, docking, and fusion of intracellular vesicles for exocytotic release of neurotransmitters and hormones. In secretory neurons and neuroendocrine cells, some voltage-gated channels are physically coupled with SNARE proteins, resulting in alterations in channel gating and trafficking. Coupling of SNARE proteins to membrane ion channels is however not unique to secretory cells. We have demonstrated the expression of SNARE proteins in rodent myocardial tissue, and more importantly, functional interaction of SNARE proteins with cardiac K_ATP and K_v (K_v1.2, K_v2.1, K_v4.2, K_v4.3, and K_v11.1) channels. SNARE proteins, therefore, have similar fundamental functions in ion channel trafficking and regulation per se, independent of secretion. We now review the body of work of SNARE protein regulation on membrane ion channels in the heart.
Cardiac atria are the primary source of ANP release in hypoxia-adapted rats
2010, Life Sciences
Citation Excerpt :
Under baseline conditions, ANP and ANP mRNA levels in the cardiac atria are 1–2 orders of magnitude greater than in the ventricles. The cardiac atria synthesize large quantities of ANP that are stored in secretory granules and secreted via a regulatory pathway, whereas the ventricles secrete ANP via a constitutive pathway and have little pre-synthesized ANP stores (Bloch et al. 1986). Thus, under normal conditions the atria are considered the primary source of ANP release (Ruskoaho et al. 1987).
Atrial natriuretic peptide (ANP) is released from the heart in response to hypoxia and helps mitigate the development of pulmonary hypertension. However, the mechanism of hypoxia-induced ANP release is not clear. The cardiac atria are the primary source of ANP secretion under normal conditions, but right ventricular ANP expression is markedly up-regulated during adaptation to hypoxia. We sought to better understand mechanisms of cardiac ANP release during adaptation to hypoxia.
We measured hypoxia-induced ANP release from isolated perfused rat hearts obtained from normoxia and hypoxia-adapted rats before and after removal of the atria.
In both normoxia- and hypoxia-adapted hearts, ANP levels in the perfusate increased within 15 min of hypoxia. Hypoxia-induced ANP release was greater from hypoxia-adapted than normoxia-adapted hearts. Baseline and hypoxia-induced ANP release were considerably greater with the atria intact (213 ± 29 to 454 ± 62 and 281 ± 26 to 618 ± 87 pg/ml for normoxia- and hypoxia-adapted hearts respectively, P < 0.001 for both) than with atria removed (94 ± 17 to 131 ± 32 and 103 ± 26 to 201 ± 55 pg/ml, respectively, P < 0.002 for both). Hypoxia-induced ANP release was reduced over 80% by removing the atria in both normoxia- and in hypoxia-adapted hearts. Acute hypoxia caused a transient increase in lactate release and reductions in pH and left ventricular generated force, but no differences in pH or left ventricular generated force were seen between normoxia- and hypoxia-adapted rats.
We conclude that the right ventricle is not a major source of cardiac ANP release in normoxia- or hypoxia-adapted rats.

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Cell

ArticleNeonatal atria and ventricles secrete atrial natriuretic factor via tissue-specific secretory pathways

Abstract

Biochem. Biophys. Res. Commun.

Cell

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Anal. Biochem.

Biochem. Biophys. Res. Commun.

J. Mol. Cell. Cardiol.

Biosynthesis and secretion of proatrial natriuretic factor by cultured rat cardiocytes

Science

Atrial natriuretic factor biosynthesis: A serum protease cleaves proANF into a 14-kilodalton peptide and ANF

Am. J. Physiol.

Immunocytochemical localization of atrial natriuretic factor in the heart and salivary glands

Histochemistry

Atrial natriuretic factor: a hormone produced by the heart

Science

Specific granules in atrial muscle cells

J. Cell Biol.

Article
Neonatal atria and ventricles secrete atrial natriuretic factor via tissue-specific secretory pathways