Skip to main content
British Heart Journal logoLink to British Heart Journal
. 1988 Oct;60(4):267–274. doi: 10.1136/hrt.60.4.267

Localisation of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the human fetal and adult heart.

J Wharton 1, R H Anderson 1, D Springall 1, R F Power 1, M Rose 1, A Smith 1, R Espejo 1, A Khaghani 1, J Wallwork 1, M H Yacoub 1, et al.
PMCID: PMC1216572  PMID: 2973340

Abstract

Atrial natriuretic peptide immunoreactivity was found in ventricular and atrial tissues with specific antisera raised to the amino and carboxy terminal regions of the precursor molecule. In 13 developing human hearts (7-24 weeks' gestation) the immunoreactivity was concentrated in the atrial myocardium and ventricular conduction system but it was also detected in the early fetal ventricular myocardium. Immunoreactivity in five normal adults was largely confined to the atrial myocardium although it was also found in the ventricular conduction tissues of hearts removed from 10 patients who were undergoing cardiac transplantation. The ventricular conduction system is an extra-atrial site for the synthesis of atrial natriuretic peptide. In the failing heart this synthesis may be further supplemented by expression of the gene in the ventricular myocardium. It is possible that ventricular production of the peptide contributes to the raised circulating concentrations of atrial natriuretic peptide immunoreactivity found in severe congestive heart disease, particularly in patients with dilated cardiomyopathy.

Full text

PDF
267

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson J. V., Christofides N. D., Vinas P., Wharton J., Varndell I. M., Polak J. M., Bloom S. R. Radioimmunoassay of alpha rat atrial natriuretic peptide. Neuropeptides. 1986 Feb-Mar;7(2):159–173. doi: 10.1016/0143-4179(86)90092-2. [DOI] [PubMed] [Google Scholar]
  2. Back H., Stumpf W. E., Ando E., Nokihara K., Forssmann W. G. Immunocytochemical evidence for CDD/ANP-like peptides in strands of myoendocrine cells associated with the ventricular conduction system of the rat heart. Anat Embryol (Berl) 1986;175(2):223–226. doi: 10.1007/BF00389598. [DOI] [PubMed] [Google Scholar]
  3. Björklund H., Hoffer B., Olson L., Palmer M., Seiger A. Enkephalin immunoreactivity in iris nerves: distribution in normal and grafted irides, persistence and enhanced fluorescence after denervations. Histochemistry. 1984;80(1):1–7. doi: 10.1007/BF00492763. [DOI] [PubMed] [Google Scholar]
  4. Bloch K. D., Seidman J. G., Naftilan J. D., Fallon J. T., Seidman C. E. Neonatal atria and ventricles secrete atrial natriuretic factor via tissue-specific secretory pathways. Cell. 1986 Dec 5;47(5):695–702. doi: 10.1016/0092-8674(86)90512-x. [DOI] [PubMed] [Google Scholar]
  5. Bouvagnet P., Neveu S., Montoya M., Leger J. J. Development changes in the human cardiac isomyosin distribution: an immunohistochemical study using monoclonal antibodies. Circ Res. 1987 Sep;61(3):329–336. doi: 10.1161/01.res.61.3.329. [DOI] [PubMed] [Google Scholar]
  6. Cantin M., Ding J., Thibault G., Gutkowska J., Salmi L., Garcia R., Genest J. Immunoreactive atrial natriuretic factor is present in both atria and ventricles. Mol Cell Endocrinol. 1987 Jul;52(1-2):105–113. doi: 10.1016/0303-7207(87)90103-1. [DOI] [PubMed] [Google Scholar]
  7. Cramb G., Banks R., Rugg E. L., Aiton J. F. Actions of atrial natriuretic peptide (ANP) on cyclic nucleotide concentrations and phosphatidylinositol turnover in ventricular myocytes. Biochem Biophys Res Commun. 1987 Nov 13;148(3):962–970. doi: 10.1016/s0006-291x(87)80226-7. [DOI] [PubMed] [Google Scholar]
  8. Day M. L., Schwartz D., Wiegand R. C., Stockman P. T., Brunnert S. R., Tolunay H. E., Currie M. G., Standaert D. G., Needleman P. Ventricular atriopeptin. Unmasking of messenger RNA and peptide synthesis by hypertrophy or dexamethasone. Hypertension. 1987 May;9(5):485–491. doi: 10.1161/01.hyp.9.5.485. [DOI] [PubMed] [Google Scholar]
  9. Ding J., Thibault G., Gutkowska J., Garcia R., Karabatsos T., Jasmin G., Genest J., Cantin M. Cardiac and plasma atrial natriuretic factor in experimental congestive heart failure. Endocrinology. 1987 Jul;121(1):248–257. doi: 10.1210/endo-121-1-248. [DOI] [PubMed] [Google Scholar]
  10. Eliska O., Elisková M. Venous circulation of the human cardiac conduction system. Br Heart J. 1979 Nov;42(5):508–513. doi: 10.1136/hrt.42.5.508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gardner D. G., Gertz B. J., Hane S. Thyroid hormone increases rat atrial natriuretic peptide messenger ribonucleic acid accumulation in vivo and in vitro. Mol Endocrinol. 1987 Mar;1(3):260–265. doi: 10.1210/mend-1-3-260. [DOI] [PubMed] [Google Scholar]
  12. Gulbenkian S., Wharton J., Polak J. M. The visualisation of cardiovascular innervation in the guinea pig using an antiserum to protein gene product 9.5 (PGP 9.5). J Auton Nerv Syst. 1987 Mar;18(3):235–247. doi: 10.1016/0165-1838(87)90122-6. [DOI] [PubMed] [Google Scholar]
  13. Haimoto H., Takahashi Y., Koshikawa T., Nagura H., Kato K. Immunohistochemical localization of gamma-enolase in normal human tissues other than nervous and neuroendocrine tissues. Lab Invest. 1985 Mar;52(3):257–263. [PubMed] [Google Scholar]
  14. Hamid Q., Wharton J., Terenghi G., Hassall C. J., Aimi J., Taylor K. M., Nakazato H., Dixon J. E., Burnstock G., Polak J. M. Localization of atrial natriuretic peptide mRNA and immunoreactivity in the rat heart and human atrial appendage. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6760–6764. doi: 10.1073/pnas.84.19.6760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hassall C. J., Wharton J., Gulbenkian S., Anderson J. V., Frater J., Bailey D. J., Merighi A., Bloom S. R., Polak J. M., Burnstock G. Ventricular and atrial myocytes of newborn rats synthesise and secrete atrial natriuretic peptide in culture: light- and electron-microscopical localisation and chromatographic examination of stored and secreted molecular forms. Cell Tissue Res. 1988 Jan;251(1):161–169. doi: 10.1007/BF00215461. [DOI] [PubMed] [Google Scholar]
  16. Hood W. B., Jr Regional venous drainage of the human heart. Br Heart J. 1968 Jan;30(1):105–109. doi: 10.1136/hrt.30.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kikuchi K., Nakao K., Hayashi K., Morii N., Sugawara A., Sakamoto M., Imura H., Mikawa H. Ontogeny of atrial natriuretic polypeptide in the human heart. Acta Endocrinol (Copenh) 1987 Jun;115(2):211–217. doi: 10.1530/acta.0.1150211. [DOI] [PubMed] [Google Scholar]
  18. Kuro-o M., Tsuchimochi H., Ueda S., Takaku F., Yazaki Y. Distribution of cardiac myosin isozymes in human conduction system. Immunohistochemical study using monoclonal antibodies. J Clin Invest. 1986 Feb;77(2):340–347. doi: 10.1172/JCI112310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lattion A. L., Michel J. B., Arnauld E., Corvol P., Soubrier F. Myocardial recruitment during ANF mRNA increase with volume overload in the rat. Am J Physiol. 1986 Nov;251(5 Pt 2):H890–H896. doi: 10.1152/ajpheart.1986.251.5.H890. [DOI] [PubMed] [Google Scholar]
  20. Maldonado C. A., Saggau W., Forssmann W. G. Cardiodilatin-immunoreactivity in specific atrial granules of human heart revealed by the immunogold stain. Anat Embryol (Berl) 1986;173(3):295–298. doi: 10.1007/BF00318912. [DOI] [PubMed] [Google Scholar]
  21. Matsubara H., Hirata Y., Yoshimi H., Takata S., Takagi Y., Yamane Y., Umeda Y., Nishikawa M., Inada M. Ventricular myocytes from neonatal rats are more responsive to dexamethasone than atrial myocytes in synthesis of atrial natriuretic peptide. Biochem Biophys Res Commun. 1987 Nov 13;148(3):1030–1038. doi: 10.1016/s0006-291x(87)80235-8. [DOI] [PubMed] [Google Scholar]
  22. Meleagros L., Ghatei M. A., Anderson J. V., Wharton J., Taylor K. M., Krikler D. M., Meijler F. L., Polak J. M., Bloom S. R. The presence and molecular forms of cardiodilatin immunoreactivity in the human and rat right atrium. Clin Chim Acta. 1988 Mar 15;172(2-3):199–209. doi: 10.1016/0009-8981(88)90324-5. [DOI] [PubMed] [Google Scholar]
  23. Nemer M., Lavigne J. P., Drouin J., Thibault G., Gannon M., Antakly T. Expression of atrial natriuretic factor gene in heart ventricular tissue. Peptides. 1986 Nov-Dec;7(6):1147–1152. doi: 10.1016/0196-9781(86)90145-2. [DOI] [PubMed] [Google Scholar]
  24. Richards A. M., Cleland J. G., Tonolo G., McIntyre G. D., Leckie B. J., Dargie H. J., Ball S. G., Robertson J. I. Plasma alpha natriuretic peptide in cardiac impairment. Br Med J (Clin Res Ed) 1986 Aug 16;293(6544):409–412. doi: 10.1136/bmj.293.6544.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Roy D., Paillard F., Cassidy D., Bourassa M. G., Gutkowska J., Genest J., Cantin M. Atrial natriuretic factor during atrial fibrillation and supraventricular tachycardia. J Am Coll Cardiol. 1987 Mar;9(3):509–514. doi: 10.1016/s0735-1097(87)80042-6. [DOI] [PubMed] [Google Scholar]
  26. Saito Y., Nakao K., Arai H., Sugawara A., Morii N., Yamada T., Itoh H., Shiono S., Mukoyama M., Obata K. Atrial natriuretic polypeptide (ANP) in human ventricle. Increased gene expression of ANP in dilated cardiomyopathy. Biochem Biophys Res Commun. 1987 Oct 14;148(1):211–217. doi: 10.1016/0006-291x(87)91097-7. [DOI] [PubMed] [Google Scholar]
  27. Scott J. N., Jennes L. Distribution of atrial natriuretic factor in fetal rat atria and ventricles. Cell Tissue Res. 1987 May;248(2):479–481. doi: 10.1007/BF00218216. [DOI] [PubMed] [Google Scholar]
  28. Smith A., Ho S. Y., Anderson R. H. Histological study of the cardiac conducting system as a routine procedure. Med Lab Sci. 1977 Jul;34(3):223–229. [PubMed] [Google Scholar]
  29. Thompson R. J., Doran J. F., Jackson P., Dhillon A. P., Rode J. PGP 9.5--a new marker for vertebrate neurons and neuroendocrine cells. Brain Res. 1983 Nov 14;278(1-2):224–228. doi: 10.1016/0006-8993(83)90241-x. [DOI] [PubMed] [Google Scholar]
  30. Thompson R. P., Simson J. A., Currie M. G. Atriopeptin distribution in the developing rat heart. Anat Embryol (Berl) 1986;175(2):227–233. doi: 10.1007/BF00389599. [DOI] [PubMed] [Google Scholar]
  31. Tikkanen I., Fyhrquist F., Metsärinne K., Leidenius R. Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers. Lancet. 1985 Jul 13;2(8446):66–69. doi: 10.1016/s0140-6736(85)90178-3. [DOI] [PubMed] [Google Scholar]
  32. Toshimori H., Toshimori K., Oura C., Matsuo H. Immunohistochemistry and immunocytochemistry of atrial natriuretic polypeptide in porcine heart. Histochemistry. 1987;86(6):595–601. doi: 10.1007/BF00489553. [DOI] [PubMed] [Google Scholar]
  33. Tsuchimochi H., Yazaki Y., Ohno H., Takanashi R., Takaku F. Ventricular expression of atrial natriuretic peptide. Lancet. 1987 Aug 8;2(8554):336–337. doi: 10.1016/s0140-6736(87)90926-3. [DOI] [PubMed] [Google Scholar]
  34. Vassall-Adams P. R. Ultrastructure of the human atrioventricular conduction tissues. Eur Heart J. 1983 Jul;4(7):449–460. doi: 10.1093/oxfordjournals.eurheartj.a061501. [DOI] [PubMed] [Google Scholar]
  35. Wei Y. F., Rodi C. P., Day M. L., Wiegand R. C., Needleman L. D., Cole B. R., Needleman P. Developmental changes in the rat atriopeptin hormonal system. J Clin Invest. 1987 May;79(5):1325–1329. doi: 10.1172/JCI112957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wharton J., Gulbenkian S. Peptides in the mammalian cardiovascular system. Experientia. 1987 Jul 15;43(7):821–832. doi: 10.1007/BF01945360. [DOI] [PubMed] [Google Scholar]

Articles from British Heart Journal are provided here courtesy of BMJ Publishing Group

RESOURCES