Basic Research in Cardiology

, Volume 91, Issue 4, pp 319–328 | Cite as

Contribution of the ventricles and the atrial appendages to the elevation of plasma atrial natriuretic factor (ANF) during pacing-induced heart failure in conscious dogs

  • W. Shen
  • X. Xu
  • M. Ochoa
  • G. A. Zeballos
  • J. M. Stewart
  • T. H. Hintze
Original Contribution


The goal of our study was to determine whether the elevation in plasma ANF was produced by the atrial appendages or ventricular tissue during pacing-induced heart failure in chronically instrumented conscious dogs (sham) or dogs with bilateral atrial appendectomy. Acute volume expansion caused a significant elevation of plasma ANF from 80±8 to 149±26 pg/ml (p<0.01) in sham dogs, but caused no significant change from 67±7 to 84±8 pg/ml in atrial appendectomized dogs. There were increases in left ventricular end-diastolic pressure (LVEDP) and left atrial pressure (LAP) in both groups of dogs. After rapid left ventricular pacing (210–240 beats/min) for 4 weeks to induce heart failure, dogs in both groups had tachycardia, elevated LVEDP and higher LAP. Plasma ANF was increased by 250% to 283±64 pg/ml (p<0.01) in sham dogs, and only 40% to 94±15 pg/ml (p>0.05) in atrial appendectomized dogs. In response to volume expansion, there were further increases in LVEDP and LAP in both groups of dogs, but plasma ANF was not elevated (288±39 pg/ml) in sham dogs and only slightly increased (132±7 pg/ml) in atrial appendectomized dogs. Our results suggest that, during pacing-induced heart failure, the atrial appendages are the major source of elevated plasma ANF, and the remaining atrial and ventricular tissue, even when maximally stretched, can only modestly increase plasma ANF.

Key words

Atrial natriuretic factor (ANF) atrial function volume expansion heart failure ventricular compliance 


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  1. 1.
    Benjamin BA, Metzler CH, Peterson TV (1987) Renal response to volume expansion in atrial appendectomized dogs. Am J Physiol 253:R786-R793Google Scholar
  2. 2.
    Benjamin BA, Meltzer CH, Peterson TV (1988) Chronic atrial appendectomy alters sodium excretion in conscious monkey. Am J Physiol 254:R695-R705Google Scholar
  3. 3.
    Bilder GE, Sweet CS, Emmert SE, Schofield TL, Edina R, Stabilito II, Friedman PA (1989) Cardiac and non-cardiac atrial natriuretic factor (ANF) biosynthesis and storage and plasma ANF in the rat model of chronic ventricular dysfunction. Endocrinology 124:1515–1521Google Scholar
  4. 4.
    Bloch KD, Seidman JC, Naftilan JD, Fallon JT, Seidman C (1986) Neonatal atria and ventricles secrete atrial natriuretic factor via tissue-specific secretory pathways. Cell 47:695–702Google Scholar
  5. 5.
    Brenner BM, Ballermann BJ, Gunning ME, Zeidel ML (1990) Diverse biological actions of atrial natriuretic peptide. Physiol Rew 70:665–699Google Scholar
  6. 6.
    Cantin M, Genest J (1985) The heart and atrial natriuretic factor. Endocr Rev 6:107–127Google Scholar
  7. 7.
    Cantin M, Thibault G, Ding J, Gutkowska J, Garcia R, Jasmin G, Hamet P, Genest J (1988) ANF in experimental congestive heart failure. Am J Pathol 130:552–568Google Scholar
  8. 8.
    Chapeau C, Gutkowsak J, Schiller PW, Milne RW, Thibault G, Garcia J, Cantin M (1985) Localization of immunoreactive synthetic atrial natriuretic factor (ANF) in the heart of various animal species. J Histochem Cytochem 33:541–550Google Scholar
  9. 9.
    Chien YW, Barbee RW, MacPhee AA, Frohlich ED, Trippodo NC (1988) Increased ANF secretion after volume expansion is preserved in rats with heart failure. Am J Physiol 254:R185-R191Google Scholar
  10. 10.
    Chow E, Woodara JC, Farrar DJ (1990) Rapid ventricular pacing in pigs. An experimental model of congestive heart failure. Am J Physiol 258:1603–1605Google Scholar
  11. 11.
    Coleman HN, Taylor RR, Pool PE, Whipple CH, Covell JW, Ross J, Braunwald E (1971) Congestive heart failure following chronic tachycardia. Am Heart J 81:790–798Google Scholar
  12. 12.
    Cowley AW Jr, Anderas PR, Skelton MM (1988) Acute saline loading in normal and bilaterally atrial-resected conscious dogs. Am J Physiol 255:H144-H152Google Scholar
  13. 13.
    De Bold AJ (1985) Atrial natriuretic factor. A hormone produced by the heart. Science (Wash. DC) 230:767–770Google Scholar
  14. 14.
    Ding J, Thibault G, Gutkowska J, Garcia R, Karabatsos Jasmin GT, Genest J, Cantin M (1987) Cardiac and plasma atrial natriuretic factor in experimental congestive heart failure. Endocrinology 121:248–257Google Scholar
  15. 15.
    Douglas PS, Morrow R, Ioli A, Reichek N (1989) Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy. J Am Coll Cardiol 13: 311–315Google Scholar
  16. 16.
    Edwards BS, Ackermann DM, Lee ME, Reeder GS, Wold LE, Burnett JC Jr (1988) Identification of atrial natriuretic factor within ventricular tissue in hamsters and humans with congestive heart failure. J Clin Invest 81:82–86Google Scholar
  17. 17.
    Edwards BS, Zimmermann RS, Schwab TR, Heublein DM, Burnett JC (1988) Atrial stretch not pressure is the principal determinant controlling the acute release of atrial natriuretic peptide. Circ Res 56:191–195Google Scholar
  18. 18.
    Franch HA, Dixon RAF, Blaine EH, Siegl PKS (1988) Ventricular atrial natriuretic factor in the cardiomyopathic hamster model of congestive heart failure. Circ Res 62:31–36Google Scholar
  19. 19.
    Genest J, Cantin M (1987) Atrial natriuretic factor. Circulation 75 (Suppl I): 118–124Google Scholar
  20. 20.
    Gould KL, Lipscomb K, Hamilton GW, Kennedy JW (1974) Relation of left ventricular shape, function and wall stress in man. Am J Cardiol 34:627–634Google Scholar
  21. 21.
    Hintze TH, McIntyre JJ, Patel MB, Shapiro JT, DeLeonardis M, Zeballos GA, Loud A (1989) Atrial wall function and plasma atriopeptin during volume expansion in conscious dogs. Am J Physiol 256:H713-H719Google Scholar
  22. 22.
    Hintze TH, Wang J, Patel M, Schustek M, Ochoa M, Dean R, Chiruzzo F, Zeballos GA (1990) Dynamics of atrial peptide secretion in the coronary circulation of the conscious dog. Circ Res 67: 609–614Google Scholar
  23. 23.
    Hoffman A, Keiser RH (1990) Conscious atrial appendectomized rats have a blunted atrial natriuretic factor release to volume expansion but normal responses to other acute stimuli. Am J Hypertension 3:786–788Google Scholar
  24. 24.
    Kinter LB, Kopia G, DePalma D, Brennan F, Landi M, Inagami T (1986) Chronic bilateral atrial appendectomy does not affect salt excretion in dogs. J Hypertens 4 (Suppl 5):S80-S82Google Scholar
  25. 25.
    Metzler CH, Lee M, Thrasher TN, Ramsay DJ (1986) Increase right or left atrial pressure release of atrial natriuretic peptide in conscious dogs. Endocrinology 119:2396–2398Google Scholar
  26. 26.
    Moe GW, Grima EA, Angus C, Wong NLM, Hu DCK, Howard RJ, Armstrong PW (1991) Response of atrial natriuretic factor to acute and chronic increases of atrial pressures in experimental heart failure in dogs. Role of changes in heart rate, atrial dimension, and cardiac tissue concentration. Circulation 83:1780–1787Google Scholar
  27. 27.
    Perrella MA, Schwab TR, O'Murchu B, Redfield MM, Wei CM, Edwards BS, Burnett Jr JC (1992) Cardiac atrial natriuretic factor during evolution of congestive heart failure. Am J Physiol 262:1248–1255Google Scholar
  28. 28.
    Redfield MM, Edwards BS, McGoon MD, Heublein DM, Aarhus LL, Burnett Jr JC (1989) Failure of atrial natriuretic factor to increase with volume expansion in acute and chronic congestive heart failure in the dog. Circulation 80:651–657Google Scholar
  29. 29.
    Saito Y, Nakao K, Arai H, Nishimura K, Okumura K, Obata K, Takemura G, Fujiwara H, Sugawara A, Yamada T, Itoh H, Mukoyama M, Hosoda K, Kawai C, Ban T, Yasue H, Imura H (1989) Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart. J Clin Invest 83: 298–305Google Scholar
  30. 30.
    Salazar FJ, Romero JC, Burnett JC Jr, Schryver S, Granger GP (1986) Atrial natriuretic peptide levels during acute and chronic saline loading in conscious dogs. Am J Physiol 251:R499-R503Google Scholar
  31. 31.
    Shannon RP, Komamura K, Stambler BS, Bigaud M, Manders WT, Vatner SF (1991) Alterations in myocardial contractility in conscious dogs with dilated cardiomyopathy. Am J Physiol 260: 1903–1911Google Scholar
  32. 32.
    Stewart JM, O'Dea DJ, Shapiro GC, Patel MB, McIntyre JT, Gewitz MH, Hoegler CT, Shapiro JT, Zeballos GA, Hintze TH (1991) Atrial compliance determines the nature of passive atrial stretch and plasma atrial natriuretic factor in the conscious dog. Cardiovascular Res 25:784–792Google Scholar
  33. 33.
    Stewart JM, Dean R, Brown M, Diasparra D, Zeballos GA, Schustek M, Gewitz MH, Thompson CI, Hintze TH (1992) Bilateral atrial appendectomy abolishes increased plasma atrial natriuretic peptide release and blunts sodium and water excretion during volume loading in conscious dogs. Circ Res 70:724–732Google Scholar
  34. 34.
    Takemura G, Fujiwara H, Horike K, Mukoyama M, Saito Y, Nakao K, Matsuda M, Kawamura A, Ishida M, Kida M, Uegaito T, Tanaka M, Matsumori A, Fujiwara Y, Fujiwara T, Imura H, Kawai C (1989) Ventricular expression of atrial natriuretic polypeptide and its relations with hemodynamics and histology in dilated human hearts, Immunohistochemical study of the endomyocardial biopsy specimens. Circulation 80:1137–1147Google Scholar
  35. 35.
    Tsuchimochi H, Kurimoto F, Ieke K, Koyama H, Takaku F, Kawana M, Kimata S, Yazaki Y (1988) Atrial natriuretic peptide distribution in fetal and failed adult human heart. Circulation 78:920–927Google Scholar
  36. 36.
    Wei Y, Rodi CP, Day ML, Wiegand RC, Needleman LD, Cole BR, Needleman P (1987) Developmental changes in the rat atriopeptin hormonal system. J Clin Invest 79:1325–1329Google Scholar
  37. 37.
    Yasue H, Obata K, Okumura K, Kurose M, Ogawa H, Matsuyama K, Jougasaki M, Saito Y, Nakao K, Imura H (1989) Increased secretion of atrial natriuretic polypeptide from the left ventricle in patients with dilated cardiomyopathy. J Clin Invest 83:46–51Google Scholar

Copyright information

© Steinkopff Verlag 1996

Authors and Affiliations

  • W. Shen
    • 1
  • X. Xu
    • 1
  • M. Ochoa
    • 1
  • G. A. Zeballos
    • 1
  • J. M. Stewart
    • 2
  • T. H. Hintze
    • 1
  1. 1.Department of PhysiologyNew York Medical CollegeValhallaUSA
  2. 2.Department of PediatricsNew York Medical CollegeValhallaUSA

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