Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Jul;86(1):52–59. doi: 10.1172/JCI114714

Prostaglandins regulate the synthesis and secretion of the atrial natriuretic peptide.

D G Gardner 1, H D Schultz 1
PMCID: PMC296689  PMID: 2142168

Abstract

We have examined the effects of several PGs on the synthesis and release of the atrial natriuretic peptide (ANP) in vivo and in vitro. PGF2 alpha infusion in anesthetized rats resulted in a significant increase in plasma immunoreactive (ir) ANP levels in vivo despite effecting only modest changes in hemodynamics. The PGs were also effective at promoting irANP secretion in primary cultures of neonatal rat atrial and ventricular cardiocytes. PGF2 alpha increased irANP release with half-maximal induction seen at approximately 10(-8) M; PGE2 was somewhat less effective and prostacyclin (PGI2) was without effect. The PGs also increased ANP mRNA levels in these cells, suggesting that these agents exert a major effect on the synthesis as well as the secretion of the prohormone. Transient expression analysis of atrial cells transfected with 2,500 bp of human (h) ANP 5' flanking sequence linked to a chloramphenicol acetyltransferase (CAT) reporter demonstrated that PGF2 alpha (10(-5) M) increased hANP promoter activity approximately twofold relative to the control. PGF2 alpha had no effect on the promoterless control (pSV0-lamin CAT). Treatment of cultured atriocytes with high concentrations of a cyclooxygenase inhibitor resulted in a significant suppression of ANP secretion in vitro and a truncation of the plasma ANP response to volume infusion in vivo. Taken together these studies support a role for PGs as regulators of cardiac ANP synthesis and secretion, and suggest an additional mechanism whereby eicosanoids may act to control cardiovascular and renal homeostasis.

Full text

PDF
52

Images in this article

Selected References

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

  1. Ahumada G. G., Sobel B. E., Needleman P. Synthesis of prostaglandins by cultured rat hearts myocytes and cardiac mesenchymal cells. J Mol Cell Cardiol. 1980 Jul;12(7):685–700. doi: 10.1016/0022-2828(80)90099-1. [DOI] [PubMed] [Google Scholar]
  2. Ballerman B. J., Brenner B. M. Biologically active atrial peptides. J Clin Invest. 1985 Dec;76(6):2041–2048. doi: 10.1172/JCI112206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ballermann B. J., Bloch K. D., Seidman J. G., Brenner B. M. Atrial natriuretic peptide transcription, secretion, and glomerular receptor activity during mineralocorticoid escape in the rat. J Clin Invest. 1986 Sep;78(3):840–843. doi: 10.1172/JCI112650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bauer R. F., Arthur L. O., Fine D. L. Propagation of mouse mammary tumor cell lines and production of mouse mammary tumor virus in a serum-free medium. In Vitro. 1976 Aug;12(8):558–563. doi: 10.1007/BF02797439. [DOI] [PubMed] [Google Scholar]
  5. Bloch K. D., Scott J. A., Zisfein J. B., Fallon J. T., Margolies M. N., Seidman C. E., Matsueda G. R., Homcy C. J., Graham R. M., Seidman J. G. Biosynthesis and secretion of proatrial natriuretic factor by cultured rat cardiocytes. Science. 1985 Dec 6;230(4730):1168–1171. doi: 10.1126/science.2933808. [DOI] [PubMed] [Google Scholar]
  6. Bolton H. S., Chanderbhan R., Bryant R. W., Bailey J. M., Weglicki W. B., Vahouny G. V. Prostaglandin synthesis by adult heart myocytes. J Mol Cell Cardiol. 1980 Nov;12(11):1287–1298. doi: 10.1016/0022-2828(80)90072-3. [DOI] [PubMed] [Google Scholar]
  7. Cantin M., Genest J. The heart and the atrial natriuretic factor. Endocr Rev. 1985 Spring;6(2):107–127. doi: 10.1210/edrv-6-2-107. [DOI] [PubMed] [Google Scholar]
  8. Dobner P. R., Kawasaki E. S., Yu L. Y., Bancroft F. C. Thyroid or glucocorticoid hormone induces pre-growth-hormone mRNA and its probable nuclear precursor in rat pituitary cells. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2230–2234. doi: 10.1073/pnas.78.4.2230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Evers A. S., Dunkel C. G., Saffitz J. E., Needleman P. Exaggerated atrial arachidonate metabolism in rabbit left ventricular myocardial infarction. J Clin Invest. 1987 Jan;79(1):155–162. doi: 10.1172/JCI112777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gaillard C. A., Koomans H. A., Rabelink A. J., Mees E. J. Effects of indomethacin on renal response to atrial natriuretic peptide. Am J Physiol. 1987 Nov;253(5 Pt 2):F868–F873. doi: 10.1152/ajprenal.1987.253.5.F868. [DOI] [PubMed] [Google Scholar]
  11. Gardner D. G., Gertz B. J., Deschepper C. F., Kim D. Y. Gene for the rat atrial natriuretic peptide is regulated by glucocorticoids in vitro. J Clin Invest. 1988 Oct;82(4):1275–1281. doi: 10.1172/JCI113726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Glembotski C. C., Gibson T. R. Molecular forms of immunoactive atrial natriuretic peptide released from cultured rat atrial myocytes. Biochem Biophys Res Commun. 1985 Nov 15;132(3):1008–1017. doi: 10.1016/0006-291x(85)91907-2. [DOI] [PubMed] [Google Scholar]
  14. Gordon R. D., Tunny T. J., Klemm S. A. Indomethacin and atrial natriuretic peptide in Bartter's syndrome. N Engl J Med. 1986 Aug 14;315(7):459–459. doi: 10.1056/NEJM198608143150716. [DOI] [PubMed] [Google Scholar]
  15. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Halushka P. V., Wohltmann H., Privitera P. J., Hurwitz G., Margolius H. S. Bartter's syndrome: urinary prostaglandin E-like material and kallikrein; indomethacin effects. Ann Intern Med. 1977 Sep;87(3):281–286. doi: 10.7326/0003-4819-87-3-281. [DOI] [PubMed] [Google Scholar]
  17. Kuehl F. A., Jr, Humes J. L. Direct evidence for a prostaglandin receptor and its application to prostaglandin measurements (rat-adipocytes-antagonists-analogues-mouse ovary assay). Proc Natl Acad Sci U S A. 1972 Feb;69(2):480–484. doi: 10.1073/pnas.69.2.480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. LaPointe M. C., Wu J. P., Greenberg B., Gardner D. G. Upstream sequences confer atrial-specific expression on the human atrial natriuretic factor gene. J Biol Chem. 1988 Jul 5;263(19):9075–9078. [PubMed] [Google Scholar]
  19. Ladenson P. W., Bloch K. D., Seidman J. G. Modulation of atrial natriuretic factor by thyroid hormone: messenger ribonucleic acid and peptide levels in hypothyroid, euthyroid, and hyperthyroid rat atria and ventricles. Endocrinology. 1988 Jul;123(1):652–657. doi: 10.1210/endo-123-1-652. [DOI] [PubMed] [Google Scholar]
  20. Lang R. E., Thölken H., Ganten D., Luft F. C., Ruskoaho H., Unger T. Atrial natriuretic factor--a circulating hormone stimulated by volume loading. Nature. 1985 Mar 21;314(6008):264–266. doi: 10.1038/314264a0. [DOI] [PubMed] [Google Scholar]
  21. Metzler C. H., Lee M. E., Thrasher T. N., Ramsay D. J. Increased right or left atrial pressure stimulates release of atrial natriuretic peptides in conscious dogs. Endocrinology. 1986 Nov;119(5):2396–2398. doi: 10.1210/endo-119-5-2396. [DOI] [PubMed] [Google Scholar]
  22. Miyamori I., Ikeda M., Matsubara T., Okamoto S., Koshida H., Yasuhara S., Morise T., Takeda R. The renal, cardiovascular and hormonal actions of human atrial natriuretic peptide in man; effects of indomethacin. Br J Clin Pharmacol. 1987 Apr;23(4):425–431. doi: 10.1111/j.1365-2125.1987.tb03071.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pohl U., Dézsi L., Simon B., Busse R. Selective inhibition of endothelium-dependent dilation in resistance-sized vessels in vivo. Am J Physiol. 1987 Aug;253(2 Pt 2):H234–H239. doi: 10.1152/ajpheart.1987.253.2.H234. [DOI] [PubMed] [Google Scholar]
  24. Potter H., Weir L., Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. doi: 10.1073/pnas.81.22.7161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Quadt J. F., Voss R., ten Hoor F. Prostacyclin production of the isolated pulsatingly perfused rat aorta. J Pharmacol Methods. 1982 Jun;7(4):263–270. doi: 10.1016/0160-5402(82)90079-1. [DOI] [PubMed] [Google Scholar]
  26. Salazar F. J., Bolterman R., Fiksen-Olsen M. J., Quesada T., Romero J. C. Role of prostaglandins in mediating the renal effects of atrial natriuretic factor. Hypertension. 1988 Sep;12(3):274–278. doi: 10.1161/01.hyp.12.3.274. [DOI] [PubMed] [Google Scholar]
  27. Sasaki H., Okumura M., Kawasaki T., Kangawa K., Matsuo H. Indomethacin and atrial natriuretic peptide in pseudo-Bartter's syndrome. N Engl J Med. 1987 Jan 15;316(3):167–167. doi: 10.1056/NEJM198701153160314. [DOI] [PubMed] [Google Scholar]
  28. Schiebinger R. J., Baker M. Z., Linden J. Effect of adrenergic and muscarinic cholinergic agonists on atrial natriuretic peptide secretion by isolated rat atria. Potential role of the autonomic nervous system in modulating atrial natriuretic peptide secretion. J Clin Invest. 1987 Dec;80(6):1687–1691. doi: 10.1172/JCI113258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schiebinger R. J., Linden J. The influence of resting tension on immunoreactive atrial natriuretic peptide secretion by rat atria superfused in vitro. Circ Res. 1986 Jul;59(1):105–109. doi: 10.1161/01.res.59.1.105. [DOI] [PubMed] [Google Scholar]
  30. Simpson P., Savion S. Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells. Cross-striations, ultrastructure, and chronotropic response to isoproterenol. Circ Res. 1982 Jan;50(1):101–116. doi: 10.1161/01.res.50.1.101. [DOI] [PubMed] [Google Scholar]
  31. Sonnenberg H., Veress A. T. Cellular mechanism of release of atrial natriuretic factor. Biochem Biophys Res Commun. 1984 Oct 30;124(2):443–449. doi: 10.1016/0006-291x(84)91573-0. [DOI] [PubMed] [Google Scholar]
  32. Thamsborg G., Keller N., Sykulski R., Storm T. Dynamic exercise stimulates ANF secretion by mechanisms independent of prostaglandins. Horm Metab Res. 1988 Feb;20(2):131–132. doi: 10.1055/s-2007-1010775. [DOI] [PubMed] [Google Scholar]
  33. Tunny T. J., Gordon R. D. Plasma atrial natriuretic peptide in primary aldosteronism (before and after treatment) and in Bartter's and Gordon's syndromes. Lancet. 1986 Feb 1;1(8475):272–273. doi: 10.1016/s0140-6736(86)90805-6. [DOI] [PubMed] [Google Scholar]
  34. Wong K. R., Xie M. H., Shi L. B., Liu F. Y., Huang C. L., Gardner D. G., Cogan M. G. Urinary cGMP as biological marker of the renal activity of atrial natriuretic factor. Am J Physiol. 1988 Dec;255(6 Pt 2):F1220–F1224. doi: 10.1152/ajprenal.1988.255.6.F1220. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES