Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Jan;85(1):115–120. doi: 10.1172/JCI114400

Atrial natriuretic peptide attenuates the development of pulmonary hypertension in rats adapted to chronic hypoxia.

H Jin 1, R H Yang 1, Y F Chen 1, R M Jackson 1, S Oparil 1
PMCID: PMC296394  PMID: 2136863

Abstract

To test the hypothesis that chronic infusion of atrial natriuretic peptide (ANP) instituted before hypoxic exposure attenuates the development of pulmonary hypertension in hypoxia adapted rats, ANP (0.2 and 1.0 microgram/h) or vehicle was administered intravenously via osmotic minipump for 4 wk beginning before exposure to 10% O2 or to room air. Low dose ANP increased plasma ANP levels by only 60% of vehicle controls after 4 wk and significantly decreased mean pulmonary arterial pressure (MPAP) (P less than 0.01), the ratio of right ventricular weight to body weight (RV/BW) (P less than 0.01), and the wall thickness of small (50-100 microns) pulmonary arteries (P = 0.01) in hypoxia-adapted rats. ANP did not alter any of these parameters in air-control rats. High dose ANP increased plasma ANP levels by 230% of control and produced greater reductions in MPAP (P less than 0.001) and RV/BW) (P less than 0.05), but not in pulmonary arterial wall thickness, than the low dose. Neither dose of ANP altered mean systemic arterial pressure in either hypoxic or normoxic rats. The data demonstrate that chronic infusion of exogenous ANP at a dose that does not affect MPAP or RV weight in air-control rats attenuates the development of pulmonary hypertension and RV enlargement in rats adapted to chronic hypoxia.

Full text

PDF

Selected References

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

  1. Abraham A. S., Kay J. M., Cole R. B., Pincock A. C. Haemodynamic and pathological study of the effect of chronic hypoxia and subsequent recovery of the heart and pulmonary vasculature of the rat. Cardiovasc Res. 1971 Jan;5(1):95–102. doi: 10.1093/cvr/5.1.95. [DOI] [PubMed] [Google Scholar]
  2. Adnot S., Chabrier P. E., Andrivet P., Viossat I., Piquet J., Brun-Buisson C., Gutkowska Y., Braquet P. Atrial natriuretic peptide concentrations and pulmonary hemodynamics in patients with pulmonary artery hypertension. Am Rev Respir Dis. 1987 Oct;136(4):951–956. doi: 10.1164/ajrccm/136.4.951. [DOI] [PubMed] [Google Scholar]
  3. Adnot S., Chabrier P. E., Brun-Buisson C., Viossat I., Braquet P. Atrial natriuretic factor attenuates the pulmonary pressor response to hypoxia. J Appl Physiol (1985) 1988 Nov;65(5):1975–1983. doi: 10.1152/jappl.1988.65.5.1975. [DOI] [PubMed] [Google Scholar]
  4. Almeida F. A., Suzuki M., Maack T. Atrial natriuretic factor increases hematocrit and decreases plasma volume in nephrectomized rats. Life Sci. 1986 Sep 29;39(13):1193–1199. doi: 10.1016/0024-3205(86)90351-6. [DOI] [PubMed] [Google Scholar]
  5. Baertschi A. J., Hausmaninger C., Walsh R. S., Mentzer R. M., Jr, Wyatt D. A., Pence R. A. Hypoxia-induced release of atrial natriuretic factor (ANF) from the isolated rat and rabbit heart. Biochem Biophys Res Commun. 1986 Oct 15;140(1):427–433. doi: 10.1016/0006-291x(86)91108-3. [DOI] [PubMed] [Google Scholar]
  6. Bianchi C., Gutkowska J., Thibault G., Garcia R., Genest J., Cantin M. Radioautographic localization of 125I-atrial natriuretic factor (ANF) in rat tissues. Histochemistry. 1985;82(5):441–452. doi: 10.1007/BF02450479. [DOI] [PubMed] [Google Scholar]
  7. Breuhaus B. A., Saneii H. H., Brandt M. A., Chimoskey J. E. Atriopeptin II lowers cardiac output in conscious sheep. Am J Physiol. 1985 Dec;249(6 Pt 2):R776–R780. doi: 10.1152/ajpregu.1985.249.6.R776. [DOI] [PubMed] [Google Scholar]
  8. Chien Y. W., Frohlich E. D., Trippodo N. C. Atrial natriuretic peptide increases resistance to venous return in rats. Am J Physiol. 1987 May;252(5 Pt 2):H894–H899. doi: 10.1152/ajpheart.1987.252.5.H894. [DOI] [PubMed] [Google Scholar]
  9. Eskay R., Zukowska-Grojec Z., Haass M., Dave J. R., Zamir N. Circulating atrial natriuretic peptides in conscious rats: regulation of release by multiple factors. Science. 1986 May 2;232(4750):636–639. doi: 10.1126/science.2938258. [DOI] [PubMed] [Google Scholar]
  10. Ignarro L. J., Wood K. S., Harbison R. G., Kadowitz P. J. Atriopeptin II relaxes and elevates cGMP in bovine pulmonary artery but not vein. J Appl Physiol (1985) 1986 Apr;60(4):1128–1133. doi: 10.1152/jappl.1986.60.4.1128. [DOI] [PubMed] [Google Scholar]
  11. Jansen T. L., Morice A. H., Brown M. J. A comparison of the vasodilator responses to atrial peptides in the pulmonary and renal arteries of the pig in vitro. Br J Pharmacol. 1987 Jul;91(3):687–691. doi: 10.1111/j.1476-5381.1987.tb11263.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jin H. K., Yang R. H., Thornton R. M., Chen Y. F., Jackson R., Oparil S. Atrial natriuretic peptide lowers pulmonary arterial pressure in hypoxia-adapted rats. J Appl Physiol (1985) 1988 Oct;65(4):1729–1735. doi: 10.1152/jappl.1988.65.4.1729. [DOI] [PubMed] [Google Scholar]
  13. Kleinert H. D., Volpe M., Odell G., Marion D., Atlas S. A., Camargo M. J., Laragh J. H., Maack T. Cardiovascular effects of atrial natriuretic factor in anesthetized and conscious dogs. Hypertension. 1986 Apr;8(4):312–316. doi: 10.1161/01.hyp.8.4.312. [DOI] [PubMed] [Google Scholar]
  14. Lang R. E., Unger T., Ganten D. Atrial natriuretic peptide: a new factor in blood pressure control. J Hypertens. 1987 Jun;5(3):255–271. doi: 10.1097/00004872-198706000-00001. [DOI] [PubMed] [Google Scholar]
  15. Lappe R. W., Smits J. F., Todt J. A., Debets J. J., Wendt R. L. Failure of atriopeptin II to cause arterial vasodilation in the conscious rat. Circ Res. 1985 Apr;56(4):606–612. doi: 10.1161/01.res.56.4.606. [DOI] [PubMed] [Google Scholar]
  16. Larose P., Meloche S., du Souich P., Deléan A., Ong H. Radioimmunoassay of atrial natriuretic factor: human plasma levels. Biochem Biophys Res Commun. 1985 Jul 31;130(2):553–558. doi: 10.1016/0006-291x(85)90452-8. [DOI] [PubMed] [Google Scholar]
  17. McKenzie J. C., Tanaka I., Inagami T., Misono K. S., Klein R. M. Alterations in atrial and plasma atrial natriuretic factor (ANF) content during development of hypoxia-induced pulmonary hypertension in the rat. Proc Soc Exp Biol Med. 1986 Mar;181(3):459–463. doi: 10.3181/00379727-181-rc3. [DOI] [PubMed] [Google Scholar]
  18. Pegram B. L., Trippodo N. C., Natsume T., Kardon M. B., Frohlich E. D., Cole F. E., MacPhee A. A. Hemodynamic effects of atrial natriuretic hormone. Fed Proc. 1986 Aug;45(9):2382–2386. [PubMed] [Google Scholar]
  19. Rabinovitch M., Gamble W., Nadas A. S., Miettinen O. S., Reid L. Rat pulmonary circulation after chronic hypoxia: hemodynamic and structural features. Am J Physiol. 1979 Jun;236(6):H818–H827. doi: 10.1152/ajpheart.1979.236.6.H818. [DOI] [PubMed] [Google Scholar]
  20. Sakamoto M., Nakao K., Morii N., Sugawara A., Yamada T., Itoh H., Shiono S., Saito Y., Imura H. The lung as a possible target organ for atrial natriuretic polypeptide secreted from the heart. Biochem Biophys Res Commun. 1986 Mar 13;135(2):515–520. doi: 10.1016/0006-291x(86)90024-0. [DOI] [PubMed] [Google Scholar]
  21. Stockmann P. T., Will D. H., Sides S. D., Brunnert S. R., Wilner G. D., Leahy K. M., Wiegand R. C., Needleman P. Reversible induction of right ventricular atriopeptin synthesis in hypertrophy due to hypoxia. Circ Res. 1988 Jul;63(1):207–213. doi: 10.1161/01.res.63.1.207. [DOI] [PubMed] [Google Scholar]
  22. Tanaka I., Misono K. S., Inagami T. Atrial natriuretic factor in rat hypothalamus, atria and plasma: determination by specific radioimmunoassay. Biochem Biophys Res Commun. 1984 Oct 30;124(2):663–668. doi: 10.1016/0006-291x(84)91606-1. [DOI] [PubMed] [Google Scholar]
  23. Trippodo N. C., Cole F. E., Frohlich E. D., MacPhee A. A. Atrial natriuretic peptide decreases circulatory capacitance in areflexic rats. Circ Res. 1986 Sep;59(3):291–296. doi: 10.1161/01.res.59.3.291. [DOI] [PubMed] [Google Scholar]
  24. Volpe M., Sosa R. E., Müller F. B., Camargo M. J., Glorioso N., Laragh J. H., Maack T., Atlas S. A. Differing hemodynamic responses to atrial natriuretic factor in two models of hypertension. Am J Physiol. 1986 May;250(5 Pt 2):H871–H878. doi: 10.1152/ajpheart.1986.250.5.H871. [DOI] [PubMed] [Google Scholar]
  25. Weselcouch E. O., Humphrey W. R., Aiken J. W. Effect of pulmonary and renal circulations on activity of atrial natriuretic factor. Am J Physiol. 1985 Nov;249(5 Pt 2):R595–R602. doi: 10.1152/ajpregu.1985.249.5.R595. [DOI] [PubMed] [Google Scholar]

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

RESOURCES