Summary
Atrial natriuretic peptide (ANP), a cardiac hormone, is known to be located in the atrial specific granules, but its presence and localization in the ventricular muscle of the human heart has not been examined fully. Using a specific antibody to human ANP, we studied the conduction system and ventricular muscle with immunohistochemical and ultrastructural methods in 30 hearts obtained at autopsy. These included 12 normal and 18 diseased hearts. In the normal hearts, ANP-positive granules, which were regularly observed in the atrial myocytes, were found in small quantities in the cells of the penetrating and branching bundles in 4 of 12, and in the cells of the ventricular free walls in 2 of the 12 hearts. In the diseased hearts, the positivity increased significantly (P<0.05), being found in 13 of 18 (72.2%) conduction systems and 10 of 18 (55.6%) ventricular muscles. The granules were confirmed to be immunoreactive with ANP by ultrastructural examination. Furthermore, the presence of ANP mRNA in the conduction system as well as in the ventricular myocytes was demonstrated by Northern blot hybridization for which we used the complementary DNA of human ANP. Thus, a small quantity of ANP appears to be synthesized and stored in the conduction system and ventricles of some normal hearts. However, ANP was shown to be present in a larger percentage of the diseased hearts.
Similar content being viewed by others
References
Anderson RH, Ho SY, Becker AE (1987) Gross anatomy and microscopy of the conduction system. In: Mandel WJ (ed) Cardiac arrhythmias, 2nd edn. Lippincott, Philadelphia, pp 13–52
Ballermann BJ, Brenner BM (1986) Role of atrial peptides in body fluid homeostasis. Circ Res 58:619–630
Cantin M, Gutkowska J, Thibault G, Milne RW, Ledoux S, Min Li S, Chapeau C, Garcia R, Hamet P, Genest J (1985) Immunocytochemical localization of atrial natriuretic factor in the heart and salivary glands. Histochemistry 80:825–832
Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159
Davies MJ, Anderson RH, Becker AE (1983) Ultrastructural investigation of the atrioventricular conduction tissues. In: Davies MJ (ed) The conduction system of the heart. Butterworths, London, pp 48–52
Day ML, Schwartz D, Wiegand RC, Stockman PT, Brunnert SR, Tolunay E, Currie MG, Standaert DG, Needleman P (1987) Ventricular atriopeptin. Unmasking of messenger RNA and peptide synthesis by hypertrophy or dexamethasone. Hypertension 9:485–491
Ding J, Thibault G, Gutkowska J, Garcia R, Karabatsos T, Jasmin G, Genest J, Cantin M (1987) Cardiac and plasma atrial natriuretic factor in experimental congestive heart failure. Endocrinology 121:248–257
Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13
Forssman WG (1986) Cardiac hormones. I. Review on the morphology, biochemistry, and molecular biology of the endocrine heart. Eur J Clin Invest 16:439–451
Gardner DG, Hane S, Trachewsky D, Schenk D, Baxter JD (1986) Atrial natriuretic peptide mRNA is regulated by glucocorticoids in vivo. Biochem Biophys Res Commun 139:1047–1054
Hamid Q, Wharton J, Terenghi G, Hassall CJS, Aimi J, Taylor KM, Nakazato H, Dixon JE, Burnstock G, Polak JM (1987) Localization of atrial natriuretic peptide mRNA and immunoreactivity in the rat heart and human appendage. Proc Natl Acad Sci USA 84:6760–6764
Hsu S-M, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580
Kangawa K, Matsuo H (1984) Purification and complete amino acid sequence ofα-human atrial natriuretic polypeptide (α-ANP). Biochem Biophys Res Commun 118:131–139
Kangawa K, Fukuda A, Kubota I, Hayashi Y, Matsuo H (1984) Identification in rat atrial tissue of multiple forms of natriuretic polypeptides of about 3000 daltons. Biochem Biophys Res Commun 121:585–591
Kangawa K, Fukuda A, Matsuo H (1985) Structural identification of β- and γ-human atrial natriuretic polypeptides. Nature 313:397–400
Kawata M, Ueda S, Nakao K, Morii N, Kiso Y, Imura H, Sano Y (1985) Immunohistochemical demonstration of α-atrial natriuretic polypeptide-containing neurons in the rat brain. Histochemistry 83:1–3
Kistin AD (1949) Observations of the anatomy of the atrioventricular bundle (bundle of HIS) and the question of other muscular connections in normal human hearts. Am Heart J 37:849–867
Komuro I, Nomoto K, Sugiyama T, Kurabayashi M, Takaku F, Yazaki Y (1987) Isolation and characterization of myosin heavy chain isozymes of the bovine conduction system. Circ Res 61:859–865
Lang RE, Thölken H, Ganten D, Luft FC, Ruskoaho H, Unger T (1985) Atrial natriuretic factor — a circulating hormone stimulated by volume loading. Nature 314:264–266
Maki M, Takayanagi R, Misono KS, Pandey KN, Tibbetts C, Inagami T (1984) Structure of rat atrial natriuretic factor precursor deduced from cDNA sequence. Nature 309:722–724
McKenzie JC, Tanaka I, Misono KS, Inagami T (1985) Immunocytochemical localization of atrial natriuretic factor in the kidney, adrenal medulla, pituitary and atrium of rat. J Histochem Cytochem 33:825–832
Miyata A, Kangawa K, Toshimori T, Hatoh T, Matsuo H (1985) Molecular forms of atrial natriuretic polypeptides in mammalian tissues and plasma. Biochem Biophys Res Commun 129:248–255
Nakao K, Sugawara A, Morii N, Sakamoto M, Suda M, Soneda J, Ban T, Kihara M, Yamori Y, Shimokura M, Kiso Y, Imura H (1984) Radioimmunoassay for α human and rat atrial natriuretic polypeptide. Biochem Biophys Res Commun 124:815–821
Nemer M, Lavigne J-P, Drouin J, Thibault G, Gannon M, Antakly T (1986) Expression of atrial natriuretic factor gene in heart ventricular tissue. Peptides 7:1147–1152
Oikawa S, Imai M, Ueno A, Tanaka S, Noguchi T, Nakazato H, Kangawa K, Fukuda A, Matsuo H (1984) Cloning and sequence analysis of cDNA encoding a precursor for human atrial natriuretic polypeptide. Nature 309:724–726
Osame M, Matsumota M, Usuku K, Izumo S, Ijichi N, Amitani H, Tara M, Igata A (1987) Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemia-like cells. Ann Neurol 21:117–122
Ruskoaho H, Leppäluoto J (1988) Immunoreactive atrial natriuretic peptide in ventricles, atria, hypothalamus, and plasma of genetically hypertensive rats. Circ Res 62:384–394
Saito Y, Nakao K, Arai H, Sugawara A, Morii N, Yamada T, Itoh H, Shiono S, Mukoyama M, Obata K, Yasue H, Ohkubo H, Nakanishi S, Imura H (1987) Atrial natriuretic polypeptide (ANP) in human ventricle. Increased gene expression of ANP in dilated cardiomyopathy. Biochem Biophys Res Commun 148:211–217
Saper CB, Standaert DG, Currie MG, Schwartz D, Geller DM, Needleman P (1985) Atriopeptin-immunoreactive neurons in the brain. Presence in cardiovascular regulatory areas. Science 227:1047–1049
Sherf L, James TN (1979) Fine structure of cells and their histologic organization within internodal pathways of the heart: clinical and electrocardiographic implications. Am J Cardiol 44:345–369
Skowsky WR, Fisher DA (1972) The use of thyroglobulin to induce antigenicity to small molecules. J Lab Clin Med 80:134–144
Sudoh T, Kangawa K, Minamino N, Matsuo H (1988) A new natriuretic peptide in porcine brain. Nature 332:78–81
Sugawara A, Nakao K, Kono T, Morii N, Yamada T, Itoh H, Shiono S, Saito Y, Mukoyama M, Arai H, Imura H (1988) Atrial natriuretic factor in essential hypertension and adrenal disorders. Hypertension 11 [Suppl I]:212–216
Tikkanen I, Fyhrguist F, Metsärinne K, Leidenius R (1985) Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers. Lancet II:66–69
Toshimori H, Toshimori K, Oura C, Matsuo H (1987) Immunohistochemistry and immunocytochemistry of atrial natriuretic polypeptide in porcine heart. Histochemistry 86:595–601
Toshimori H, Toshimori K, Oura C, Matsuo H, Matsukura S (1988) The distribution of atrial natriuretic polypeptide (ANP)-containing cells in the adult rat heart. Anat Embryol 177:477–484
Weidmann P, Matter DR, Matter EE, Gnädinger MP, Uehlinger DE, Shaw S, Hess C (1988) Glucocorticoid and mineralocorticoid stimulation of atrial natriuretic peptide release in man. J Clin Endocrinol Metab 66:1233–1239
Wharton J, Anderson RH, Springgall D, Power RT, Rose M, Smith A, Espejo R, Khaghni A, Wallwork J, Yacoub MH, Polak JM (1988) Localization of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the fetal and adult heart. Br Heart J 60:267–274
Widran J, Lev M (1951) The dissection of the atrioventricular node, bundle and bundle branches in the human heart. Circulation 4:864–867
Yamaji T, Ishibashi M, Nakaoka H, Imataka K, Amano M, Fujii J (1985a) Possible role for atrial natriuretic peptide in polyuria associated with paroxysmal atrial arrhythmias. Lancet I:1211
Yamaji T, Ishibashi M, Takaku F (1985b) Atrial natriuretic factor in human blood. J Clin Invest 76:1705–1709
Yamaji T, Ishibashi M, Sekihara H, Takaku F, Nakaoka H, Fujii J (1986) Plasma levels of atrial natriuretic peptide in primary aldosteronism and essential hypertension. J Clin Endocrinol Metab 63:815–818
Yamanaka M, Greenberg B, Johnson L, Seilhamer J, Brewer M, Friedemann T, Miller J, Atlas S, Laragh J, Lewicki J, Fiddes J (1984) Cloning and sequence analysis of the cDNA for the rat atrial natriuretic factor precursor. Nature 309:719–722
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mochizuki, N., Sawa, H., Yasuda, H. et al. Distribution of atrial natriuretic peptide in the conduction system and ventricular muscles of the human heart. Vichows Archiv A Pathol Anat 418, 9–16 (1991). https://doi.org/10.1007/BF01600239
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01600239