Skip to main content
SpringerLink
Log in

Pharmacological Modification of the ANP System

  • Conference paper
Book cover Endocrinology of the Heart

  • 81 Accesses

Summary

The search for drugs interacting with the ANP system to give favourable therapeutic effects has concentrated on the release and the metabolism of ANP. Regarding the release of ANP direct effects have to be distinguished from indirect ones. Both drug induced increases and decreases of ANP plasma levels may be indirectly mediated: Increased ANP plasma levels are noted after sodium retaining antihypertensives such as reserpine and minoxidil. On the other hand, the pathological high ANP plasma levels of SHR are normalized in parallel to the amelioration of cardiac hypertrophy by the natriuretic calcium antagonist nitrendipine. The mechanism for β-blocker-induced increase in plasma ANP is not clear as yet.

Direct effects on ANP release can be demonstrated using in vitro assays of isolated atria. An increase of ANP has been reported for agents increasing the intracellular calcium concentration such as the calcium agonist BAY K 8644, the newly discovered endogenous vasoconstrictor endothelin or the protein kinase C activator TPA. These effects can be antagonized by calcium antagonists, but calcium antagonists have no effect on baseline ANP release, and a reduction in intracellular or extracellular calcium has also been reported to increase ANP release in vitro.

A direct stimulatory effect on ANP release of isolated rat atria was found with the endogenous opioid peptide dynorphin. In contrast, the increase in ANP plasma levels after high dose of morphine seems to be mediated by the central nervous system.

For natriuretic drugs antagonization of ANP by monoclonal antibodies is another way to detect mechanisms of action involving endogenous ANP. Although the effects of exogenous and endogenous ANP were effectively blocked by the antibody in vivo, no diminution of the natriuretic effects of calcium antagonists or clonidine in rats could be observed.

Research in the metabolism of ANP has led to the discovery that enkephalinase inhibitors prolong the half life of ANP and enhance the effects of ANP. The therapeutic relevance of this mechanism has to be evaluated.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Baranowska B, Gutkowska J, Talbot P, Genest J, Cantin M (1987) Plasma immunoreactive atrial natriuretic factor is inhibited by selective blockade of alpha2 adrenergic receptors in conscious Sprague-Dawley rats. Neurose Lett 76: 119–123

    Article  CAS  Google Scholar 

  2. de Bold A (1987) Functional morphology of the endocrine component of the heart. In: Brenner M, Laragh JH (eds) Biologically active atrial peptides, vol 1. American Society of Hypertension Symposium Series, Raven Press, New York

    Google Scholar 

  3. Crum RL, Brown MR (1988) Effects of morphine and opioid peptides on plasma levels of atrial natriuretic peptides. Life Sci 43: 851–858

    Article  PubMed  CAS  Google Scholar 

  4. Frelin C, Vigne P, Barbry P, Lazdunski M (1987) Molecular properties of amiloride action and of its Na+ transporting targets. Kidney Int 32: 785–793

    Article  PubMed  CAS  Google Scholar 

  5. Fukuda Y, Hirata Y, Yoshimi H, Kojima T, Kobayashi Y, Yanagisawa M, Masaki T (1988) Endothelin is a potent secretagogue for atrial natriuretic peptide in cultured rat atrial myocytes. Biochem Biophys Res Commun 155: 167–172

    Article  PubMed  CAS  Google Scholar 

  6. Goldstein A (1983) Biology and chemistry of the dynorphin peptides. In: Meienhofer J, Udenfried S (eds) The peptides: analysis synthesis biology, vol 7. Academic Press, New York

    Google Scholar 

  7. Greenwald JE, Apkon M, Sides SD, Needleman P (1988) Cellular mechanisms regulating atriopeptin release. J Cell Biochem [Suppl] 12A: 4

    Google Scholar 

  8. Gutkowska J, Racz K, Garcia R, Thibault G, Kuchel O, Genest J, Cantin M (1986) The morphine effect on plasma ANF. Eur J Pharmacol 131: 91–94

    Article  PubMed  CAS  Google Scholar 

  9. Haufe MC, Gerzer R, Weil J, Ernst JG, Theisen K (1988) Verapamil impairs secretion of stimulated atrial natriuretic factor in humans. J Am Coll Cardiol 11: 1199–1203

    Article  PubMed  CAS  Google Scholar 

  10. Heim JM, Ivanova K, Gerzer R (1988) Amiloride increases the sensitivity of particulate guanylate cyclase to atrial natriuretic factor. Biochem Biophys Res Commun 152: 1263–1268

    Article  PubMed  CAS  Google Scholar 

  11. Hirn C, Stasch JP, John A, Kazda S, Morich F, Neuser D, Wohlfeil S (1986) The renal response to acute hypervolemia is caused by atrial natriuretic peptides. J Cardiovasc Pharmacol 8: 268–275

    Article  Google Scholar 

  12. Hirn C, Kauczor HK, Stasch JP, Wohlfeil S (1988) The release of atrial natriuretic peptides and its role in volume regulation. J Cell Biochem [Suppl] 12A: 8

    Google Scholar 

  13. Huidiboro-Toro JP, Parada S (1985) K-opiates and urination: Pharmacological evidence for an endogenous role of the K opiate receptor in fluid and electrolyte balance. Eur J Pharmacol 107: 1–10

    Article  Google Scholar 

  14. Lachance D, Garcia R (1988) Atrial natriuretic factor release by angiotensin II in the conscious rat. Hypertension 11: 502–508

    PubMed  CAS  Google Scholar 

  15. Leander JD (1983) A kappa opioid effect: Increased urination in the rat. J Pharmacol Exp Ther 224: 89–94

    PubMed  CAS  Google Scholar 

  16. Meloche S, McMcoll N, Lin B, Ong H, De Lean A (1988) Atrial natriuretic factor R1 receptor from Bovine adrenal zona glomerulosa: Purification, characterization and modulation by amiloide. Biochemistry 27: 8151–8158

    Article  PubMed  CAS  Google Scholar 

  17. Nakaoka H, Kitahara Y, Amano M, Imataka K, Fujii J, Ishibashi M, Yamaji T (1987) Effect of (3-adrenergic receptor blockade on atrial natriuretic peptide in essential hypertension. Hypertension 10: 221–225

    PubMed  CAS  Google Scholar 

  18. Pettersson K, Anderson J, Sjölander M, Bloom SR (1987) Atrial natriuretic peptide and the natriuresis due to acute fl-blockade in conscious hypertensive rats. Clin Exp Ther Pract A9: 95–107

    CAS  Google Scholar 

  19. Rapelli A, Dessi-Fulgheri P, Madeddu P, Glorioso N (1987) Studies on the natriuretic effect of nifedipine in hypertensive patients: Increase in levels of plasma atrial natriuretic factor without participation of the renal kallikrein-kinin system. J Hypertension 5: S61–S65

    Article  Google Scholar 

  20. Ruskoaho H, Toth M, Ganten D, Unger T, Lang RE (1986) The phorbol ester induced atrial natriuretic peptide secretion is stimulated by forskolin and BAY K 8644 and inhibited by 8 Bromo-cyclic-GMP. Biochem Biophys Res Commun 139: 266–274

    Article  PubMed  CAS  Google Scholar 

  21. Seino M, Abe K, Nushiro N, Yoshinaga K (1988) Nifedipine enhances the vasodepressor and natriuretic effects of atrial natriuretic peptide. Hypertension 11: 34–40

    PubMed  CAS  Google Scholar 

  22. Shima J, Ogihara T, Hara H, Iinuma K, Kumahara Y (1987) Effects of calcium antagonists on the secretion of atrial natriuretic peptide in normal volunteers. Curr Therap Res 42: 115–123

    Google Scholar 

  23. Sigrist G, Fuchs B, Greven J (1985) Characterization of the renal effects of an imidazothiadiazol-acrylamide derivative in rats. Naunyn-Schmiedeberg’s Arch Pharmacol 330: R31

    Google Scholar 

  24. Sonnenberg JL, Sakane Y, Jeng AY, Koehn JA, Ansell JA, Wennogle LP, Ghai RD (1988) Identification of protease 3.4.24.11 as the major atrial natriuretic factor degrading enzyme in rat kidney. Peptides 9: 173–180

    Article  PubMed  CAS  Google Scholar 

  25. Stasch JP, Kazda S, Hirn C (1987) The different effects of a calcium antagonist and a sodium retaining vasodilatator on blood pressure, cardiac hypertrophy and atrial natriuretic peptides in SHR. J Hypertens 5: S211 - S213

    CAS  Google Scholar 

  26. Stasch JP, Grote H, Kazda S, Hirn C (1989) Dynorphin stimulates release of ANP from isolated rat atria. Eur J Pharmacol (submitted)

    Google Scholar 

  27. Stephenson SL, Kenny AJ (1987) The hydrolysis of alpha-human atrial natriuretic peptide by pig kidney microvillar membranes is initiated by endopeptidase 24.11. Biochem J 243: 183–187

    PubMed  CAS  Google Scholar 

  28. Thamsborg G, Sykulski R, Larsen J, Storm T, Keller N (1987) Effect of 131 adrenoceptor blockade on plasma levels of atrial natriuretic peptide during exercise in normal man. Clin Physiol 7: 313–318

    Article  PubMed  CAS  Google Scholar 

  29. Veress AT, Milojevic S, Yip C, Flynn TG, Sonnenberg H (1988) In vitro secretion of atrial natriuretic factor: receptor-mediated release of prohormone. Am J Physiol 254: R809–814

    Google Scholar 

  30. Vollmar AM, Arendt RM, Schulz R (1987) The effect of opioids on rat plasma atrial natriuretic peptide. Eur J Pharmacol 143: 315–321

    Article  PubMed  CAS  Google Scholar 

  31. Xie CW, Yin LY, Xie XZ, Gao XM, Xia ZQ, Chang JK, Tang J (1988) A dynorphin peptide induces hypotension by stimulating the release of atrial natriuretic peptide from rat atrium. Life Sci 42: 11–17

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pharmakologie, Bayer AG, Wuppertal, Germany

    C. Hirth, J.-P. Stasch, D. Neuser & S. Kazda

Authors
  1. C. Hirth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J.-P. Stasch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Neuser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Kazda
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medizinische Klinik II und Poliklinik der Universität, Ostmerheimer Straße 200, D-5000, Köln 91, Germany

    W. Kaufmann  & G. Wambach  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Hirth, C., Stasch, JP., Neuser, D., Kazda, S. (1989). Pharmacological Modification of the ANP System. In: Kaufmann, W., Wambach, G. (eds) Endocrinology of the Heart. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-83858-3_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-83858-3_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-51409-1

  • Online ISBN: 978-3-642-83858-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation