Evaluation of plasma concentration of atrial natriuretic peptide (ANP) in horses with pulmonic valve regurgitation
Subject Areas :
Veterinary Clinical Pathology
Mohamad Hasan Najizadeh
1
,
Mohammad Reza Mokhber Dezfouli
2
,
ُSirus Sadeghian Chleshtori
3
,
Gholamreza Nikhbakht Borujeni
4
,
Alireza Vajhi
5
,
Masoumeh Jabbari Fakhr
6
,
Mohammadreza Mehrara
7
,
hossein shad
8
1 - PhD Student, Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
2 - Professor, Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran؛ Researcher of Institute of Biomedical Research, University of Tehran, Tehran, Iran.
3 - Assistant Professor, Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.؛ Researcher of Institute of Biomedical Research, University of Tehran, Tehran, Iran.
4 - Professor, Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.؛ Researcher of Institute of Biomedical Research, University of Tehran, Tehran, Iran.
5 - Professor, Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.؛ Researcher of Institute of Biomedical Research, University of Tehran, Tehran, Iran.
6 - Researcher of Institute of Biomedical Research, University of Tehran, Tehran, Iran.
7 - Private sector veterinarian.
8 - BSc of Veterinary Laboratory Science, Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Received: 2020-09-19
Accepted : 2020-12-06
Published : 2020-10-22
Keywords:
horse,
ANP,
Echocardiography,
Pulmonic valve regurgitation,
Abstract :
Atrial natriuretic peptide (ANP) is secreted by cardiac myocytes and its plasma concentration often increases in patients with cardiovascular disease in response to blood volume expansion and stretching of cardiac chambers. Increase in plasma concentration of ANP (Cp ANp ) has been observed in humans with cardiac diseases and horses with left-sided valvular disease. This study aimed to investigate plasma ANP level in horses with pulmonic valve regurgitationand its association with echocardiographic parameters. Clinical and echocardiographic examinations were performed on several jumping horses in the equestrian clubs of Tehran, Iran. Eleven horses with pulmonic valve regurgitation were identified by echocardiographic examination and were included in the case group (Group A), and 14 healthy horses were taken as the control group (Group B). Then, B-Mode, M-Mode and doppler echocardiographic parameters were measured and compared between the two groups. Blood samples from the jugular vein were collected in tubes and were transferred to laboratory. Cp ANp was measured by Sandwich ELISA method using an equine specific kit.MeanCp ANp of horses in group1 and group2 were 6.39±2.87 pg/ml and 4.78±2.45 pg/ml respectively, but no significant differences were observed. Except for right ventricular internal diameter, other echocardiographic parameters were not significantly different between the two groups. Cp ANp was significantly correlated to systolic right ventricle length and left ventricular width. In conclusionno significant differences were observed between Cp ANp of healthy horses and horses with pulmonic regurgitation. Based on the Correlation between CpANP and right ventricle length, an elevation in Cp ANp might be expected in severe pulmonic regurgitation with change in ventricle`s dimensions.
References:
Azimzadeh, K. and Hassanpour, A. (2018). Evaluation of serum homocysteine and cardiac troponin I in sheep with theileriosis in urmia city. Veterinary Clinical Pathology, 12(1): 69-77.
Brown D.J., Rush J.E., MacGregor J., Ross Jr J.N., Brewer, B. and Rand, W.M. (2003). M-mode echocardiographic ratio indices in normal dogs, cats and horses: a novel quantitative method. Journal of Veterinary Internal Medicine, 17(5): 653-662.
Cao, Z., Jia, Y. and Zhu, B. (2019). BNP and NT-proBNP as diagnostic biomarkers for cardiac dysfunction in both clinical and forensic medicine. International Journal of Molecular Science, 20(8): 1820-1824.
Casserly, B. and Klinger, J. (2009). Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent. Drug Design, Development and Therapy, 29(3): 269-287.
Cornell, C.C., Kittleson, M.D., Della Torre, P., Haggstrom, J., Lombard, C.W., Pedersen, H.D., et al. (2004). Allometric scaling of M-mode cardiac measurements in normal adult dogs. Journal of Veterinary Internal Medicine, 18(3): 311-321.
Davidson, C., Naas, A.A., Hanson, J.K., Kennedy, N.S.J., Coutie, W.J. and Struthers, A.D. (1996). Comparison of atrial natriuretic proatrial natriuretic peptide as indicators of left ventricular systolic dysfunction. American Journal of Cardiology, 77(10): 828-831.
De Bold, A.J., Borenstein, H.B., Veress, A.T. and Sonnenberg, H. (1981). A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Science, 28(1): 89-94.
Di-Angelantonio, E., Chowdhury, R., Sarwar, N., Ray, K.K., Gobin, R., Saleheen, D., et al. (2009). B-Type natriuretic peptides and cardiovascular risk systematic review and meta-analysis of 40 prospective Studies. Circulation, 120(22): 2177-2187.
Edwards, B.S., Zimmerman, R.S., Schwab, T.R., Heublein, D.M. and Burnett, J.C. (1988). Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor. Circulation Research, 62(2): 191-195.
Fartashvand, M., Derangian, A. and Kaveh, A.A. (2013). Evaluation of cardiac troponin I alteration in dairy cattle with septic metritis. Veterinary Clinical Pathology, 7(3): 239-248
Greco, D.S., Biller, B. and Liew, C.H. (2003). Measurement of plasma atrial natriuretic peptide as an indicator of prognosis in dogs with cardiac disease. Canadian Veterinary Journal, 44(4): 293-297.
Hassanpor, A. and Fartashvand, M. (2013). Serum concentration of cardiac troponin and some enzymes in horses with strangles. Veterinary Clinical Pathology, 6(4): 1703-1707.
Heishima, Y., Hori, Y., Nakamura, K., Yamashita, Y., Isayama, N., Kanno, N., et al. (2018). Diagnostic accuracy of plasma atrial natriuretic peptide concentrations in cats with and without cardiomyopathies. Journal of Veterinary Cardiology, 20(4): 234-243.
Kanno, N., Hori, Y., Hidaka, Y., Chikazawa, S., Kanai, K., Hoshi, F., et al. (2016). Plasma atrial natriuretic peptide and N-terminal pro B-type natriuretic peptide concentrations in dogs with right-sided congestive heart failure. Journal of Veterinary Medical Science, 78(4): 535-542.
Kisch, B. (1956). Electron microscopy of atrium of the heart. Experimental Medicine and Surgery, 14(2–3): 99-112.
Kobayashi, K., Hori, Y. and Chimura, S. (2014). Plasma N-terminal pro B-type natriuretic peptide concentrations in dogs with pulmonic stenosis. Journal of Veterinary Medicine, 76(6): 827-831.
Lee, H.S., Cho, K.W., Kim, H.Y. and Ahn, Y.M. (2020). Chamber-specific regulation of atrial natriuretic peptide secretion in cardiac hypertrophy: atrial wall dynamics in the ANP secretion. European Journal of Physiology, 472(5): 515-528.
Leroux, A.A., Al-Haidar, A., Remy, B., Borde, L., Cerri, S., Houben, R.M.A.C., et al. (2014). Atrial natriuretic peptide as an indicator of the severity ofvalvular regurgitation and heart failure in horses. Journal of Equine Veterinary Science, 34(10): 1226-1233.
Maisel, A.S., Duran, J.M. and Wettersten, N. (2018). Natriuretic peptide in heart failure: Atrial and B-type natriuretic peptides. Heart Failure Clinics, 14(1): 13-25.
Marino-Goulart, D., Eberle, M.C., Boudousq, V., Hejazi-Moughari, A., Piot, C., Caderes de kerleau, C., et al. (2003). Major increase in brain natriuretic peptide indicates right ventricular systolic dysfunction in patients with heart failure. European Journal of Heart Failure, 5(4): 481-488.
Meems, L.M.G. and Burnett, J.C. (2016). Innovative Therapeutics:Designer natriuretic peptides. JACC Basic to Translational Science, 1(7): 557-567.
Mukoyama, M., Obata, K. and Yasue, H. (1991). Brain natriuretic peptide as a novel cardiac hormone in humans . Evidence for an exquisite dual natriuretic peptide system , atrial natriuretic peptide and brain natriuretic peptide. The Journal of Clinical Investigation, 87(4): 1402-1412.
Nakagawa, Y., Nishikimi, T. and Kuwahara, K. (2019). Atrial and brain natriuretic peptides: Hormones secreted from the heart. Peptides Journal, 111(1): 18-25.
Pandit, K., Mukhopadhyay, P., Ghosh, S. and Chowdhury, S. (2011). Natriuretic peptides : Diagnostic and therapeutic use. Indian journal of Endocrionology and Metabolism, 15(4): 345-353.
Paolino, A., Hussain, T., Pavon, A., Velasco, M.N., Uribe, S., Ordonez, A., et al. (2017). NT-proBNP as marker of ventricular dilatation and pulmonary regurgitation after surgical correction of tetralogy of fallot : A MRI validation study. Pediatric Cardiology, 38(2): 324-331.
Park, S.Y., Lee, C.Y., Kim, C., Jang, S.H., Park, Y.B., Park, S., et al. (2015). One-year prognosis and the role of brain natriuretic peptide levels in patients with chronic cor pulmonale. Journal of Korean Medical Science, 30(4): 442-449.
Petterson, A., Hender, J., Hender, T., Held, P., Swedberg, K. and Towle, A. (1986). Increased plasma levels of atrial natriuretic peptide in patients with congestive heart failure. European Heart Journal, 7(8): 693-696.
Rostami, A., Masoudifard, M., Vajhi, A., Mokhber Dezfouli, M.R., Rezakhani, A., Tavanaeimanesh, H., et al. (2015). Echocardiographic findings in athletic horses with pulmonary regurgitation. Iranian Journal of Veterinary Medicine, 9(1): 7-12.
Song, W., Wang, H. and Wu, Q. (2016). Atrial natriuretic peptide in cardiovascular bilogy and disease. Gene, 569(1): 1-6.
Sudoh, T., Minamino, N., Kangawa, K. and Matsuo, H. (1990). C-Type natriuretic peptide (CNP): A new member of natriuretic peptide family identified in porcine brain. Biochemical and Biophysical Research Communication, 168(2): 863-870.
Tambrchi, Y., Shirani, D., Masoudifard, M., Khaki, Z., Chegini, S. and Taheri, M. (2016). Evaluation of circulating amino terminal pro-B-type natriuretic peptide concentration in cardiac valvular disease and assesing disease severity in dogs. Iranian Journal of Veterinary Research, 71(3): 365-371.
Trachsel, D.S., Grenacher, B., Weishaupt, M.A. and Schwarzwald, C.C. (2012). Plasma atrial natriuretic peptide concentrations in horses with heart disease: A pilot study. Veterinary Journal, 192(2): 166-170.
Trachsel, D.S., Grenacher, B. and Schwarzwald, C.C. (2015). Plasma atrial/A-type natriuretic peptide (ANP) concentration in horses with various heart diseases. Journal of Veterinary Cardiology, 17(3): 216-228.
Trachsel, D.S., Schwarzwald, C.C., Bitschnau, C., Grenacher, B. and Weishaupt, M.A. (2013). Atrial natriuretic peptide and cardiac troponin I concentrations in healthy Warmblood horses and in Warmblood horses with mitral regurgitation at rest and after exercise. Journal of Veterinary Cardiology, 15(2): 105-121.
Van der Vekens, N., Decloedt, A., de Clercq, D., Ven, S., Sys, S. and Van Loon, G. (2016). Atrial natriuretic peptide vs. N-terminal-pro-atrial natriuretic peptide for the detection of left atrial dilatation in horses. Equine Veterinary Journal, 48(1): 15-20.
Van der vekens, N., Decloedt, A., de Clercq, D., Ven, S. and Van Loon, G. (2015). Equine BNP measurement using a porcine BNP enzyme-linked immunoassay: A pilot study. Vlaams Diergeneeskundig Tijdschrift, 84(2): 80-87.
Van der vekens, N., Hunter, I., Timm, A., Decloedt, A., De Clercq, D., Deprez, P., et al. (2015). Total plasma proANP increases with atrial dilatation in horses. Veterinary Record, 177(24): 624-628.
Van der vekens, N., Hunter, I., Goetze, J.P., Decloedt, A., De clercq, D. and Van Loon, G. (2013). Human and equine cardiovascular endocrinology : beware to compare. Cardiovascular Endocrinology, 2(4): 67-76.
Van Kimmenade, R.R.J. and Jannuzi, J.L.J. (2009). The evolution of natriuretic peptides - current application in human and animal medicine. Journal of Veterinary Cardiology, 11(1): 9-21.
Wong, P.C.Y., Guo, J. and Zhang, A. (2017). The renal and cardiovascular effects of natriuretic peptides. Avdances in Physiology Education, 41(2): 179-185.
Woods, R.L. (2004). Cardioprotective functions of atrial natriuretic peptide and B-type natriuretic peptide: A brief review. Clinical and Experimental Pharmacology and Physiology, 31(11): 791-794.
Yoon, C.H., Zo, J.H., Kim, Y.J., Kim, H.K., Shine, D.H., Kim, K.H., et al. (2010). B-Type natriuretic peptide in isolated severe tricuspid regurgitation: determinants and impact on outcome. Journal of Cardiovascular Ultrasound, 18(4): 139-145.
Yoshimura, M., Yasue, H. and Ogawa, H. (2001). Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure. Canadian Journal of Physiology and Pahrmacology, 79(8): 730-735.
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Azimzadeh, K. and Hassanpour, A. (2018). Evaluation of serum homocysteine and cardiac troponin I in sheep with theileriosis in urmia city. Veterinary Clinical Pathology, 12(1): 69-77.
Brown D.J., Rush J.E., MacGregor J., Ross Jr J.N., Brewer, B. and Rand, W.M. (2003). M-mode echocardiographic ratio indices in normal dogs, cats and horses: a novel quantitative method. Journal of Veterinary Internal Medicine, 17(5): 653-662.
Cao, Z., Jia, Y. and Zhu, B. (2019). BNP and NT-proBNP as diagnostic biomarkers for cardiac dysfunction in both clinical and forensic medicine. International Journal of Molecular Science, 20(8): 1820-1824.
Casserly, B. and Klinger, J. (2009). Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent. Drug Design, Development and Therapy, 29(3): 269-287.
Cornell, C.C., Kittleson, M.D., Della Torre, P., Haggstrom, J., Lombard, C.W., Pedersen, H.D., et al. (2004). Allometric scaling of M-mode cardiac measurements in normal adult dogs. Journal of Veterinary Internal Medicine, 18(3): 311-321.
Davidson, C., Naas, A.A., Hanson, J.K., Kennedy, N.S.J., Coutie, W.J. and Struthers, A.D. (1996). Comparison of atrial natriuretic proatrial natriuretic peptide as indicators of left ventricular systolic dysfunction. American Journal of Cardiology, 77(10): 828-831.
De Bold, A.J., Borenstein, H.B., Veress, A.T. and Sonnenberg, H. (1981). A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Science, 28(1): 89-94.
Di-Angelantonio, E., Chowdhury, R., Sarwar, N., Ray, K.K., Gobin, R., Saleheen, D., et al. (2009). B-Type natriuretic peptides and cardiovascular risk systematic review and meta-analysis of 40 prospective Studies. Circulation, 120(22): 2177-2187.
Edwards, B.S., Zimmerman, R.S., Schwab, T.R., Heublein, D.M. and Burnett, J.C. (1988). Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor. Circulation Research, 62(2): 191-195.
Fartashvand, M., Derangian, A. and Kaveh, A.A. (2013). Evaluation of cardiac troponin I alteration in dairy cattle with septic metritis. Veterinary Clinical Pathology, 7(3): 239-248
Greco, D.S., Biller, B. and Liew, C.H. (2003). Measurement of plasma atrial natriuretic peptide as an indicator of prognosis in dogs with cardiac disease. Canadian Veterinary Journal, 44(4): 293-297.
Hassanpor, A. and Fartashvand, M. (2013). Serum concentration of cardiac troponin and some enzymes in horses with strangles. Veterinary Clinical Pathology, 6(4): 1703-1707.
Heishima, Y., Hori, Y., Nakamura, K., Yamashita, Y., Isayama, N., Kanno, N., et al. (2018). Diagnostic accuracy of plasma atrial natriuretic peptide concentrations in cats with and without cardiomyopathies. Journal of Veterinary Cardiology, 20(4): 234-243.
Kanno, N., Hori, Y., Hidaka, Y., Chikazawa, S., Kanai, K., Hoshi, F., et al. (2016). Plasma atrial natriuretic peptide and N-terminal pro B-type natriuretic peptide concentrations in dogs with right-sided congestive heart failure. Journal of Veterinary Medical Science, 78(4): 535-542.
Kisch, B. (1956). Electron microscopy of atrium of the heart. Experimental Medicine and Surgery, 14(2–3): 99-112.
Kobayashi, K., Hori, Y. and Chimura, S. (2014). Plasma N-terminal pro B-type natriuretic peptide concentrations in dogs with pulmonic stenosis. Journal of Veterinary Medicine, 76(6): 827-831.
Lee, H.S., Cho, K.W., Kim, H.Y. and Ahn, Y.M. (2020). Chamber-specific regulation of atrial natriuretic peptide secretion in cardiac hypertrophy: atrial wall dynamics in the ANP secretion. European Journal of Physiology, 472(5): 515-528.
Leroux, A.A., Al-Haidar, A., Remy, B., Borde, L., Cerri, S., Houben, R.M.A.C., et al. (2014). Atrial natriuretic peptide as an indicator of the severity ofvalvular regurgitation and heart failure in horses. Journal of Equine Veterinary Science, 34(10): 1226-1233.
Maisel, A.S., Duran, J.M. and Wettersten, N. (2018). Natriuretic peptide in heart failure: Atrial and B-type natriuretic peptides. Heart Failure Clinics, 14(1): 13-25.
Marino-Goulart, D., Eberle, M.C., Boudousq, V., Hejazi-Moughari, A., Piot, C., Caderes de kerleau, C., et al. (2003). Major increase in brain natriuretic peptide indicates right ventricular systolic dysfunction in patients with heart failure. European Journal of Heart Failure, 5(4): 481-488.
Meems, L.M.G. and Burnett, J.C. (2016). Innovative Therapeutics:Designer natriuretic peptides. JACC Basic to Translational Science, 1(7): 557-567.
Mukoyama, M., Obata, K. and Yasue, H. (1991). Brain natriuretic peptide as a novel cardiac hormone in humans . Evidence for an exquisite dual natriuretic peptide system , atrial natriuretic peptide and brain natriuretic peptide. The Journal of Clinical Investigation, 87(4): 1402-1412.
Nakagawa, Y., Nishikimi, T. and Kuwahara, K. (2019). Atrial and brain natriuretic peptides: Hormones secreted from the heart. Peptides Journal, 111(1): 18-25.
Pandit, K., Mukhopadhyay, P., Ghosh, S. and Chowdhury, S. (2011). Natriuretic peptides : Diagnostic and therapeutic use. Indian journal of Endocrionology and Metabolism, 15(4): 345-353.
Paolino, A., Hussain, T., Pavon, A., Velasco, M.N., Uribe, S., Ordonez, A., et al. (2017). NT-proBNP as marker of ventricular dilatation and pulmonary regurgitation after surgical correction of tetralogy of fallot : A MRI validation study. Pediatric Cardiology, 38(2): 324-331.
Park, S.Y., Lee, C.Y., Kim, C., Jang, S.H., Park, Y.B., Park, S., et al. (2015). One-year prognosis and the role of brain natriuretic peptide levels in patients with chronic cor pulmonale. Journal of Korean Medical Science, 30(4): 442-449.
Petterson, A., Hender, J., Hender, T., Held, P., Swedberg, K. and Towle, A. (1986). Increased plasma levels of atrial natriuretic peptide in patients with congestive heart failure. European Heart Journal, 7(8): 693-696.
Rostami, A., Masoudifard, M., Vajhi, A., Mokhber Dezfouli, M.R., Rezakhani, A., Tavanaeimanesh, H., et al. (2015). Echocardiographic findings in athletic horses with pulmonary regurgitation. Iranian Journal of Veterinary Medicine, 9(1): 7-12.
Song, W., Wang, H. and Wu, Q. (2016). Atrial natriuretic peptide in cardiovascular bilogy and disease. Gene, 569(1): 1-6.
Sudoh, T., Minamino, N., Kangawa, K. and Matsuo, H. (1990). C-Type natriuretic peptide (CNP): A new member of natriuretic peptide family identified in porcine brain. Biochemical and Biophysical Research Communication, 168(2): 863-870.
Tambrchi, Y., Shirani, D., Masoudifard, M., Khaki, Z., Chegini, S. and Taheri, M. (2016). Evaluation of circulating amino terminal pro-B-type natriuretic peptide concentration in cardiac valvular disease and assesing disease severity in dogs. Iranian Journal of Veterinary Research, 71(3): 365-371.
Trachsel, D.S., Grenacher, B., Weishaupt, M.A. and Schwarzwald, C.C. (2012). Plasma atrial natriuretic peptide concentrations in horses with heart disease: A pilot study. Veterinary Journal, 192(2): 166-170.
Trachsel, D.S., Grenacher, B. and Schwarzwald, C.C. (2015). Plasma atrial/A-type natriuretic peptide (ANP) concentration in horses with various heart diseases. Journal of Veterinary Cardiology, 17(3): 216-228.
Trachsel, D.S., Schwarzwald, C.C., Bitschnau, C., Grenacher, B. and Weishaupt, M.A. (2013). Atrial natriuretic peptide and cardiac troponin I concentrations in healthy Warmblood horses and in Warmblood horses with mitral regurgitation at rest and after exercise. Journal of Veterinary Cardiology, 15(2): 105-121.
Van der Vekens, N., Decloedt, A., de Clercq, D., Ven, S., Sys, S. and Van Loon, G. (2016). Atrial natriuretic peptide vs. N-terminal-pro-atrial natriuretic peptide for the detection of left atrial dilatation in horses. Equine Veterinary Journal, 48(1): 15-20.
Van der vekens, N., Decloedt, A., de Clercq, D., Ven, S. and Van Loon, G. (2015). Equine BNP measurement using a porcine BNP enzyme-linked immunoassay: A pilot study. Vlaams Diergeneeskundig Tijdschrift, 84(2): 80-87.
Van der vekens, N., Hunter, I., Timm, A., Decloedt, A., De Clercq, D., Deprez, P., et al. (2015). Total plasma proANP increases with atrial dilatation in horses. Veterinary Record, 177(24): 624-628.
Van der vekens, N., Hunter, I., Goetze, J.P., Decloedt, A., De clercq, D. and Van Loon, G. (2013). Human and equine cardiovascular endocrinology : beware to compare. Cardiovascular Endocrinology, 2(4): 67-76.
Van Kimmenade, R.R.J. and Jannuzi, J.L.J. (2009). The evolution of natriuretic peptides - current application in human and animal medicine. Journal of Veterinary Cardiology, 11(1): 9-21.
Wong, P.C.Y., Guo, J. and Zhang, A. (2017). The renal and cardiovascular effects of natriuretic peptides. Avdances in Physiology Education, 41(2): 179-185.
Woods, R.L. (2004). Cardioprotective functions of atrial natriuretic peptide and B-type natriuretic peptide: A brief review. Clinical and Experimental Pharmacology and Physiology, 31(11): 791-794.
Yoon, C.H., Zo, J.H., Kim, Y.J., Kim, H.K., Shine, D.H., Kim, K.H., et al. (2010). B-Type natriuretic peptide in isolated severe tricuspid regurgitation: determinants and impact on outcome. Journal of Cardiovascular Ultrasound, 18(4): 139-145.
Yoshimura, M., Yasue, H. and Ogawa, H. (2001). Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure. Canadian Journal of Physiology and Pahrmacology, 79(8): 730-735.