Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Aug;83(16):6132–6136. doi: 10.1073/pnas.83.16.6132

Atrial natriuretic factor stimulates Na/K/Cl cotransport in vascular smooth muscle cells.

M E O'Donnell, N E Owen
PMCID: PMC386453  PMID: 2942944

Abstract

Atrial natriuretic factor (ANF) is a collective term used to describe a group of peptides isolated from mammalian atria which have vasorelaxant activity as well as diuretic and natriuretic activity. Recently, ANF peptides have been shown to bind to specific receptors on vascular smooth muscle cells (VSMC) and to cause an elevation in cGMP levels. We have previously demonstrated that VSMC possess a prominent, cyclic-nucleotide-sensitive Na/K/Cl cotransport system. In the present study, the effects of the ANF peptide rat atriopeptin III (rAP III) were measured on Na/K/Cl cotransport of VSMC by using primary cultures derived from rat thoracic aorta. It was found that rAP III caused a marked elevation of Na/K/Cl cotransport. Maximal stimulation occurred at 100 nM, and the dose of rAP III required for half-maximal potassium influx (K1/2) was 9 nM. We also investigated the effect of rAP III on cGMP levels in VSMC. It was found that rAP III increased cGMP in a dose-dependent manner, with a K1/2 value of 10 nM. Finally, we measured the effect of the permeable cGMP analog 8-bromo-cGMP on Na/K/Cl cotransport. It was found that 8-bromo-cGMP stimulated cotransport to the same extent as did a saturating dose of rAP III (K1/2 = 0.2 microM). Saturating doses of rAP III and 8-Br-cGMP in combination did not stimulate cotransport in an additive manner, suggesting that rAP III probably does not elevate cGMP via inhibition of phosphodiesterase. These findings suggest that activation of Na/K/Cl cotransport via elevations in cGMP may be associated with ANF-mediated vasorelaxation and/or ANF-mediated diuresis and natriuresis.

Full text

PDF
6132

Selected References

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

  1. Blaustein M. P. Sodium ions, calcium ions, blood pressure regulation, and hypertension: a reassessment and a hypothesis. Am J Physiol. 1977 May;232(5):C165–C173. doi: 10.1152/ajpcell.1977.232.5.C165. [DOI] [PubMed] [Google Scholar]
  2. Garay R. P., Dagher G., Pernollet M. G., Devynck M. A., Meyer P. Inherited defect in a Na+, K-co-transport system in erythrocytes from essential hypertensive patients. Nature. 1980 Mar 20;284(5753):281–283. doi: 10.1038/284281a0. [DOI] [PubMed] [Google Scholar]
  3. Gargus J. J., Miller I. L., Slayman C. W., Adelberg E. A. Genetic alterations in potassium transport in L cells. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5589–5593. doi: 10.1073/pnas.75.11.5589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hamet P., Tremblay J., Pang S. C., Garcia R., Thibault G., Gutkowska J., Cantin M., Genest J. Effect of native and synthetic atrial natriuretic factor on cyclic GMP. Biochem Biophys Res Commun. 1984 Sep 17;123(2):515–527. doi: 10.1016/0006-291x(84)90260-2. [DOI] [PubMed] [Google Scholar]
  5. Harper J. F., Brooker G. Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0 acetylation by acetic anhydride in aqueous solution. J Cyclic Nucleotide Res. 1975;1(4):207–218. [PubMed] [Google Scholar]
  6. Hirata Y., Tomita M., Yoshimi H., Ikeda M. Specific receptors for atrial natriuretic factor (ANF) in cultured vascular smooth muscle cells of rat aorta. Biochem Biophys Res Commun. 1984 Dec 14;125(2):562–568. doi: 10.1016/0006-291x(84)90576-x. [DOI] [PubMed] [Google Scholar]
  7. Jayme D. W., Adelberg E. A., Slayman C. W. Reduction of K+ efflux in cultured mouse fibroblasts, by mutation or by diuretics, permits growth in K+-deficient medium. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1057–1061. doi: 10.1073/pnas.78.2.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Nakayama K., Ohkubo H., Hirose T., Inayama S., Nakanishi S. mRNA sequence for human cardiodilatin-atrial natriuretic factor precursor and regulation of precursor mRNA in rat atria. Nature. 1984 Aug 23;310(5979):699–701. doi: 10.1038/310699a0. [DOI] [PubMed] [Google Scholar]
  9. Napier M. A., Vandlen R. L., Albers-Schönberg G., Nutt R. F., Brady S., Lyle T., Winquist R., Faison E. P., Heinel L. A., Blaine E. H. Specific membrane receptors for atrial natriuretic factor in renal and vascular tissues. Proc Natl Acad Sci U S A. 1984 Oct;81(19):5946–5950. doi: 10.1073/pnas.81.19.5946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Owen N. E. Effect of TPA on ion fluxes and DNA synthesis in vascular smooth muscle cells. J Cell Biol. 1985 Aug;101(2):454–459. doi: 10.1083/jcb.101.2.454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Owen N. E., Prastein M. L. Na/K/Cl cotransport in cultured human fibroblasts. J Biol Chem. 1985 Feb 10;260(3):1445–1451. [PubMed] [Google Scholar]
  12. Owen N. E. Regulation of Na/K/Cl cotransport in vascular smooth muscle cells. Biochem Biophys Res Commun. 1984 Dec 14;125(2):500–508. doi: 10.1016/0006-291x(84)90568-0. [DOI] [PubMed] [Google Scholar]
  13. Palfrey H. C., Greengard P. Hormone-sensitive ion transport systems in erythrocytes as models for epithelial ion pathways. Ann N Y Acad Sci. 1981;372:291–308. doi: 10.1111/j.1749-6632.1981.tb15482.x. [DOI] [PubMed] [Google Scholar]
  14. Palluk R., Gaida W., Hoefke W. Atrial natriuretic factor. Life Sci. 1985 Apr 15;36(15):1415–1425. doi: 10.1016/0024-3205(85)90048-7. [DOI] [PubMed] [Google Scholar]
  15. Rao M. C., Nash N. T., Field M. Differing effects of cGMP and cAMP on ion transport across flounder intestine. Am J Physiol. 1984 Jan;246(1 Pt 1):C167–C171. doi: 10.1152/ajpcell.1984.246.1.C167. [DOI] [PubMed] [Google Scholar]
  16. Rapoport R. M., Draznin M. B., Murad F. Endothelium-dependent vasodilator-and nitrovasodilator-induced relaxation may be mediated through cyclic GMP formation and cyclic GMP-dependent protein phosphorylation. Trans Assoc Am Physicians. 1983;96:19–30. [PubMed] [Google Scholar]
  17. Rapoport R. M., Draznin M. B., Murad F. Sodium nitroprusside-induced protein phosphorylation in intact rat aorta is mimicked by 8-bromo cyclic GMP. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6470–6474. doi: 10.1073/pnas.79.21.6470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ross R. The smooth muscle cell. II. Growth of smooth muscle in culture and formation of elastic fibers. J Cell Biol. 1971 Jul;50(1):172–186. doi: 10.1083/jcb.50.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saier M. H., Jr, Boyden D. A. Mechanism, regulation and physiological significance of the loop diuretic-sensitive NaCl/KCl symport system in animal cells. Mol Cell Biochem. 1984;59(1-2):11–32. doi: 10.1007/BF00231303. [DOI] [PubMed] [Google Scholar]
  20. Solomon R., Taylor M., Dorsey D., Silva P., Epstein F. H. Atriopeptin stimulation of rectal gland function in Squalus acanthias. Am J Physiol. 1985 Sep;249(3 Pt 2):R348–R354. doi: 10.1152/ajpregu.1985.249.3.R348. [DOI] [PubMed] [Google Scholar]
  21. Steiner A. L., Parker C. W., Kipnis D. M. Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. J Biol Chem. 1972 Feb 25;247(4):1106–1113. [PubMed] [Google Scholar]
  22. Thibault G., Garcia R., Carrier F., Seidah N. G., Lazure C., Chrétien M., Cantin M., Genest J. Structure-activity relationships of atrial natriuretic factor (ANF). I. Natriuretic activity and relaxation of intestinal smooth muscle. Biochem Biophys Res Commun. 1984 Dec 28;125(3):938–946. doi: 10.1016/0006-291x(84)91374-3. [DOI] [PubMed] [Google Scholar]
  23. Winquist R. J., Faison E. P., Waldman S. A., Schwartz K., Murad F., Rapoport R. M. Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7661–7664. doi: 10.1073/pnas.81.23.7661. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES