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Vet Pathol 40:501-506 (2003)
© 2003 American College of Veterinary Pathologists

Immunohistochemistry of Atrial and Brain Natriuretic Peptides in Control Cats and Cats with Hypertrophic Cardiomyopathy

A. W. Biondo, E. J. Ehrhart, D. D. Sisson, B. J. Bulmer, H. S. A. De Morais and P. F. Solter

Departments of Veterinary Pathobiology (AWB, EJE, 1 PFS) and Veterinary Clinical Medicine (DDS, BJB), University of Illinois, Urbana, IL; and Department of Veterinary Clinical Sciences, Universidade Estadual de Londrina, Londrina, Brazil (HSAM ,2)


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Discussion
 References
 
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones involved in electrolyte and fluid homeostasis. Our laboratory has investigated the use of ANP and BNP as diagnostic markers of cardiac disease in cats. We hypothesize that the cardiac distribution of ANP and BNP increases in cats with hypertrophic cardiomyopathy (HCM). Accordingly, we evaluated the immunohistochemical distribution of ANP and BNP in hearts of four cats with naturally occurring HCM relative to five healthy controls. Indirect immunoperoxidase was performed with polyclonal immunoglobulin G against feline ANP (1–28) and proBNP (43–56). In control cats, ANP and BNP immunoreactivity was restricted to the atria. Staining for both peptides was most intense adjacent to the endocardial surface. Auricles stained more diffusely than atria for both peptides. The interstitial capillaries and nerve fibers within the heart were positive only for BNP. Atrial immunoreactivity for ANP and BNP was more diffuse and had a less distinctly layered pattern in HCM than in control cats. Ventricular cardiomyocytes of HCM cats were negative for ANP but stained lightly and diffusely for BNP. The capillaries and nerve fibers remained positive for BNP. We conclude that in cats with HCM, the cardiac distribution of ANP and BNP is more diffuse in the atria and that novel expression of BNP in the ventricular cardiomyocytes occurs.

Key words: ANP; BNP; cats; feline cardiac tissue; heart; hypertrophic cardiomyopathy; immunohistochemistry.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Discussion
 References
 
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are hormones synthesized by cardiomyocytes released into the circulation as a result of cardiac wall stretching and play a role in electrolyte-fluid homeostasis by inducing diuresis, natriuresis, and peripheral vasodilation.18 These members of the natriuretic peptide family, which also includes C-type natriuretic peptide, share similar amino acid sequences and a 17–amino acid ringlike structure resulting from the presence of an internal disulfide bond.40 Because ANP and BNP messenger RNA (mRNA) are mainly produced by the heart tissue and correlate with increases in circulating peptide levels,17,24,25,29 besides their hormonal function these peptides also have been indicated as potential markers for cardiac disease, such as congestive heart failure,1,17,23 dilated cardiomyopathy,37,41 and hypertrophic cardiomyopathy.9,15,23,34

ANP in normal hearts of cats and several other species is reportedly restricted to the atria (including the auricles), with minimal or no presence in ventricular myocytes.6,7,22,28,32 This peptide is normally stored in atrial myocardiocyte cytoplasmic granules, as observed in several species.5–7,21,22,28,32 We have sequenced and shown previously that cardiac ANP gene expression in normal cats also is restricted to the atria.3 We also have found that ANP gene expression in cats with naturally occurring hypertrophic cardiomyopathy (HCM) is maintained primarily in the atria but can be observed in variable amounts in the ventricles as well.4 Similar findings were observed in dogs and humans, where variable levels of ANP were found in ventricles of hypertrophic hearts.7,34

BNP has colocalization with ANP in the atrial cardiomyocyte granules,27 but it is also detected in normal ventricular myocytes of mice and rats.26,38 It is still controversial whether BNP is present in the ventricles of normal humans.20 BNP gene expression is reportedly restricted to the atria of normal dogs and is also present in ventricles of dogs, rabbits, and humans with heart failure.2,15,19

Although we have recently sequenced the feline BNP gene (Z. L. Liu, C. E. Wiedmeyer, D. D. Sisson, and P. F. Solter, Felis catus brain natriuretic peptide mRNA, GenBank Accession No. AF253495, 2001), the localization of its peptide product in hearts of either normal cats or cats with heart failure has not been done. Our laboratory investigated the potential use of natriuretic peptides as diagnostic tests of cardiovascular disease in cats. The purpose of this study was to determine whether a change in distribution of ANP and BNP occurs in the hearts of cats with naturally occurring HCM. We hypothesized that the histologic distribution of both hormones is more widespread within the hearts of cats with naturally occurring HCM. This could explain, at least in part, the increased plasma concentrations of ANP and BNP in cats with HCM.


   Material and Methods
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 Abstract
 Introduction
 Material and Methods
Results
 Discussion
 References
 
Animals and samples

Tissue samples were obtained from five cats free of heart disease and four cats with confirmed HCM. The cats were euthanatized for purposes unrelated to this study, by using an overdose of barbiturate and following approved guidelines for care and use. Clinical evaluation included physical examination, electrocardiography, thoracic radiography, echocardiography, blood pressure measurement, and serum T4 concentration. The diagnosis of HCM was based on the findings of a hypertrophied, nondilated left ventricle by echocardiographic evaluation and the absence of other cardiac diseases or systemic disorders (e.g., systemic hypertension or hyperthyroidism) capable of producing left ventricular hypertrophy and was confirmed on necropsy and histology.10 Full-thickness sections were removed from the free walls (middle third from apex to base) of left ventricle, right ventricle, and interventricular septum of each heart and cut into 1-cm3 pieces for fixation. The right atria and left atria, as well as the respective auricles, were separated and removed completely. All samples were placed in 4% paraformaldehyde overnight at 4 C, processed, and embedded in paraffin until immunohistochemistry was performed.

Immunohistochemistry

An avidin–biotin–peroxidase complex commercial method (DAKO Co., Carpinteria, CA) was used for immunohistochemistry. Briefly, 4-mm-thick paraffin wax sections were mounted on slides, which were dried for 30 minutes in an oven (60–70 C) and deparaffinized in xylene. The slides were then placed in changes of ethanol for 2 minutes each. Washing in buffer solution was performed between steps. The slides were then placed in two changes of 3% hydrogen peroxide and incubated in a casein-based block (Powerblock, Biogenex, San Ramon, CA). The slides were subsequently incubated in avidin block for 15 minutes, biotin block for 15 minutes, primary antibody (ANP or BNP) for 30 minutes, and biotinylated secondary antibody for 15 minutes. The reagent incubation was performed with streptavidin peroxidase for 15 minutes. A 5-minute Mayer's hematoxylin counterstain was used. The slides were dehydrated, cleared with xylene, and mounted with permanent mounting medium.

Because feline and human ANP sequences are identical,3 commercial polyclonal rabbit antibodies designed for immunohistochemistry and directed against the C-terminal human ANP (C-ANP 1–28) were obtained and used as a primary antibody (Phoenix Pharmaceuticals Inc., Belmont, CA). Specific feline BNP polyclonal rabbit antibodies directed against the N-terminal portion of feline BNP precursor peptide sequence (proBNP 43–56) (Z. L. Liu, C. E. Wiedmeyer, D. D. Sisson, and P. F. Solter, Felis catus brain natriuretic peptide mRNA, GenBank Accession number AF253495, 2001) were obtained commercially (Quality Bioresources Inc., Austin, TX). Titrational studies were conducted for both antibodies, and the optimum working concentration obtained was 1 : 1,000 for both.


   Results
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 Abstract
 Introduction
 Material and Methods
 Results
Discussion
 References
 
In all control cats, ANP and BNP immunoreactivity was restricted to the atria (Figs. 1–12). Atrial cardiomyocyte staining for ANP and BNP was more intense and diffuse adjacent to the endocardial surface as compared with the epicardial surface (Figs. 1, 4) for all cats. The auricles stained more diffusely than the atria for both peptides. None of the ventricular cardiomyocytes of control hearts stained for either ANP or BNP (Figs. 7, 10). The interstitial capillaries and nerve fibers within the heart were strongly positive for BNP (Figs. 2, 6, 10) and negative for ANP (Fig. 1)



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  		Figs. 1–12. Hearts; control cats and cats with HCM. En, endocardial surface; Ep, epicardial surface; N, nerve bundle. Avidin–biotin–peroxidase complex method. Fig. 1. Atrium; control heart, ANP. Cardiomyocytes with intense staining, adjacent to the endocardial surface, with nerves negative. Bar = 220 µm.
Fig. 2. Atrium; HCM, ANP. Immunoreactivity more diffuse and the layered pattern less distinct. Bar = 220 µm.
Fig. 3. Atrium; control, ANP. Granular distribution in the cytoplasm of cardiomyocytes. Bar = 22 µm.
Fig. 4. Atrium (same tissue block as Fig. 1); control, BNP. Cardiomyocytes staining with similar pattern to Fig. 1 but nerves staining positive. Bar = 220 µm.
Fig. 5. Atrium; HCM, BNP. Diffuse immunoreactivity with similar pattern of Fig. 2. Bar = 220 µm.
Fig 6. Atrium; control, BNP. Immunoreactivity of nerve fibers within the cardiac muscle. Bar = 22 µm.
Fig. 7. Ventricle; control, ANP. Cardiomyocytes lack staining. Bar = 220 µm.
Fig. 8. Ventricle; HCM, ANP. Cardiomyocytes lack staining. Bar = 220 µm.
Fig. 9. Ventricle; control, BNP. Negative stain control for 10–12 slides. Bar = 55 µm.
Fig. 10. Ventricle; control, BNP. Cardiomyocytes staining negative and interstitial capillaries positive (arrows). Bar = 55 µm.
Fig. 11. Ventricle; HCM, BNP. Capillaries staining positive (arrows) and cardiomyocytes with light and diffuse staining for BNP. Bar = 55 µm.
Fig. 12. Ventricle; HCM, BNP. Higher magnification of the capillary and cardiomyocyte staining. Bar = 22 µm.

 
In cats with HCM, the atrial immunoreactivity for ANP and BNP was more diffuse and the layered pattern less distinct than in controls for both (Figs. 2, 5). The HCM ventricular cardiomyocytes were negative for ANP (Fig. 8), staining lightly and diffusely for BNP (Figs. 11, 12). The capillaries and nerve fibers remained positive for BNP in HCM (Figs. 11, 12).


   Discussion
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
References
 
In this study, we have found ANP immunoreactivity in atrial cardiomyocytes of control cats as reported previously in other species.5–7,21,22,28,32 Similar to what occurs in dogs,7 rabbits,19 and humans,33,37 this reactivity was restricted to atrial cardiomyocytes with no ventricular staining. This contrasts with the distribution of ANP in rats, wherein ANP is also present in healthy ventricular cardiomyocytes.30,38 We have previously shown that feline ANP gene expression also is restricted to the atria in normal cats.3 Normal production, storage, and release to circulation of ANP in cats are likely restricted to atrial myocardiocytes, with no ventricular involvement.

We have shown previously that gene expression of ANP in cats with naturally occurring HCM is primarily in the atria but can be observed in variable amounts in the ventricles as well.4 Similar results were reported in dogs and humans, where variable amounts of ANP were found in hypertrophic hearts.7,34

Similar to what occurs in humans20 and rats31,39 but not in dogs,7 the most intense staining for ANP was found in the auricles when compared with the body of the atria. The preferential location of ANP in the auricular appendage suggests a difference in tissue production. The significance of this finding is still uncertain, maybe because of a more sensitive response to stretching stress of the auricles than to the atrial body.

In cats, atrial cardiomyocyte staining for ANP was more intense and diffuse adjacent to the endocardial surface as compared with the epicardial surface. Similar findings are reported in healthy pig and human atria,16,35,37 and in abnormal ventricles in dogs.7 Presumably, this pattern of distribution developed to facilitate endocardial release of the peptide after myocardial production.

Immunohistochemical staining of BNP was restricted to the atria in control cats. With the exception of ventricular myocytes of mice26 and rats,27 BNP was not found in the ventricle of most species that have been studied.5,18,21,40 Minute amounts of BNP were found in ventricle of dogs,2 and its localization in humans is still controversial.15,20,37 These inconsistencies in many species may result from differences in sensitivity of immunohistochemistry to the uneven tissue distribution of the peptide (demonstrated as a layered pattern with higher concentration at the endocardial side), to different affinities of the antibodies used, or to a variability in distribution of BNP in those species.

As in dogs,2 the atrial staining for BNP in control cats was more intense at the auricles. We also observed a layered pattern of atrial cardiomyocyte staining for BNP that was more intense and diffuse adjacent to the endocardial surface than at the epicardial surface. A similar pattern of distribution for BNP has been observed in humans8 and pigs.16 An analogous mechanism of peptide production and release in different myocardial layers could explain the codistribution of ANP and BNP in cat atria.

Interestingly, the nerve fibers within the hearts of the control cats stained positive for BNP. Studies performed on other species, such as cows, sheep, rats, pigs, and humans, also have shown localization of natriuretic peptides to nervous tissue in the heart or peripheral conduction system.12–14,42 The role of natriuretic peptides in cardiac conduction cells is still unclear. It is speculated that the natriuretic peptides function in an autocrine or paracrine manner to balance the cardiac conduction rate.12 The interstitial capillaries stained positive for BNP. Some investigators suggest that BNP and ANP bind to common receptors in brain capillary and aortic endothelial cells.11 Capillaries and nerve fibers remained positive for BNP in feline hearts with HCM.

In cats with HCM, the atrial walls were thicker than those of the control cats, and atrial immunoreactivity for ANP and BNP was distributed more prominently and more diffusely throughout the atria. This change may represent an increase in peptide production throughout the atrial cardiomyocytes, with increased release of natriuretic peptides. Increased ANP and BNP immunoreactivity in the atria of cats with HCM could reflect a physiologic stimulation, e.g., chronic atrial stretch caused by elevated filling pressures resulting from reduced ventricular compliance or valvular insufficiency. Alternatively, these changes could be an integral part of the underlying disease process producing myocardial hypertrophy.

In the present study we have not found ANP immunostaining in ventricles of cat hearts with HCM. However, we have previously shown variable ventricular ANP gene expression in feline cardiac tissue with HCM.4 This ventricular expression of ANP also has been reported in human dilated cardiomyopathy and cardiac infarction.33,34 In our present study, we believe that the negative immunostaining was a result of tissue ANP levels below the detectable limit or may be caused by an immediate release of ANP after transcription.

Although ventricular cardiomyocytes with HCM were negative for ANP, they stained for BNP lightly and diffusely. The presence of ventricular BNP has been observed previously in several cardiac diseases, including myocarditis,35 myocardial infarction,5 amyloidosis,36 chronic heart failure,17 dilated cardiomyopathy,37 and HCM.20,34

Tissue expression of ANP and BNP can correlate to their plasma levels, as reported previously.17 If found to be true in cats, the novel production of BNP to include the ventricles suggests that BNP could be a sensitive plasma marker of feline HCM. Moreover, the clear differences in the patterns of ANP and BNP immunostaining between the control hearts and the hearts with HCM suggest a potential use of these peptides as auxiliary markers for the histologic diagnosis of HCM. Further studies would be necessary to establish the diagnostic accuracy of these as tissue markers, particularly in their ability to differentiate HCM from other causes of cardiac hypertrophy.

In summary, cardiac ANP and BNP production/storage in healthy cats appears to be restricted to atrial cardiomyocytes, particularly those lining the endocardial surface. In addition, BNP also can be found in the interstitial capillaries and nerve fibers within the normal cat heart. In cats with spontaneously occurring HCM, ANP and BNP are more prominently and more diffusely distributed within the atria, and BNP has novel expression within the ventricle.

Parts of this article were presented at the 2002 Meeting of the American College of Veterinary Pathologists and American Society of Veterinary Clinical Pathology in New Orleans, LA.


   Acknowledgments
 
We thank Jane Chladny for help with the immunohistochemical processing. A. W. Biondo was sponsored through a research fellowship from CNPq—Brazilian National Council of Scientific and Technologic Development. This project was funded in part by a grant from the Winn Feline foundation.


   Footnotes
 
Present address: Colorado State University Veterinary Diagnostic Laboratory, Fort Collins, CO. Back

Present address: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI. Back


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Discussion
 References
 

  1. Asano K, Masuda K, Okumura M, Kadosawa T, Fujinaga T: Plasma atrial and brain natriuretic peptide levels in dogs with congestive heart failure. J Vet Med Sci 61:523-529, 1999[CrossRef][ISI][Medline]
  2. Asano K, Murakami M, Endo D, Kimura T, Fujinaga T: Complementary DNA cloning, tissue distribution, and synthesis of canine brain natriuretic peptide. Am J Vet Res 60:860-864, 1999[ISI][Medline]
  3. Biondo AW, Liu ZL, Wiedmeyer CE, de Morais HSA, Sisson DD, Solter PE: Genomic sequence and cardiac expression of atrial natriuretic peptide in cats. Am J Vet Res 63:236-240, 2002[CrossRef][ISI][Medline]
  4. Biondo AW, Wiedmeyer CE, Sisson DD, Fox PR, Solter PE: Cardiac expression of atrial natriuretic peptide gene in feline cardiomyopathy. Vet Pathol 38:151, 2001
  5. Cameron VA, Rademaker MT, Ellmers LJ, Espiner EA, Nicholls MG, Richards AM: Atrial (ANP) and brain natriuretic peptide (BNP) expression after myocardial infarction in sheep: ANP is synthesized by fibroblasts infiltrating the infarct. Endocrinology 141:4690-4697, 2000[Abstract/Free Full Text]
  6. Chapeau C, Gutkowska J, Schiller PW, Milne RW, Thibault G, Garcia R, Genest J, Cantin M: Localization of immunoreactive synthetic atrial natriuretic factor (ANF) in the heart of various animal species. J Histochem Cytochem 33:541-550, 1985[Abstract]
  7. Colbatzky F, Vollmar A, Monch U, Hermanns W: Synthesis and distribution of atrial natriuretic peptide (ANP) in hearts from normal dogs and those with cardiac abnormalities. J Comp Pathol 108:149-163, 1993[ISI][Medline]
  8. Doyama K, Fukumoto M, Takemura G, Tanaka M, Oda T, Hasegawa K, Inada T, Ohtani S, Fujiwara T, Itoh H, Nakao K, Sasayama S, Fujiwara H: Expression and distribution of brain natriuretic peptide in human right atria. J Am Coll Cardiol 32:1832-1838, 1998[Abstract/Free Full Text]
  9. Fahy GJ, McCreery CJ, O'Sullivan F, Keenan AK, Quigley PJ, Maurer BJ: Plasma atrial natriuretic peptide is elevated in patients with hypertrophic cardiomyopathy. Int J Cardiol 55:149-155, 1996[CrossRef][ISI][Medline]
  10. Fox PR: Feline cardiomyopathies. In: Textbook of Canine and Feline Cardiology, ed. Fox PR, Sisson DD, and Moise NS, 2nd ed., pp 621-678, WB Saunders, Philadelphia, PA 1999
  11. Gelfand RA, Frank HJ, Levin E, Pedram A: Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells. Am J Physiol 261:E183-E189, 1991
  12. Hansson M: Natriuretic peptides in relation to the cardiac innervation and conduction system. Microsc Res Tech 58:378-386, 2002[CrossRef][ISI][Medline]
  13. Hansson M, Eriksson A, Forsgren S: Natriuretic peptide immunoreactivity in nerve structures and Purkinje fibres of human, pig and sheep hearts. Histochem J 29:329-336, 1997[CrossRef][ISI][Medline]
  14. Hansson M, Forsgren S: Immunoreactive atrial and brain natriuretic peptides are co-localized in Purkinje fibres but not in the innervation of the bovine heart conduction system. Histochem J 27:222-230, 1995[ISI][Medline]
  15. Hasegawa K, Fujiwara H, Doyama K, Miyamae M, Fujiwara T, Suga S, Mukoyama M, Nakao K, Imura H, Sasayama S: Ventricular expression of brain natriuretic peptide in hypertrophic cardiomyopathy. Circulation 88:372-380, 1993[Abstract/Free Full Text]
  16. Hasegawa K, Fujiwara H, Itoh H, Nakao K, Fujiwara T, Imura H, Kawai C: Light and electron microscopic localization of brain natriuretic peptide in relation to atrial natriuretic peptide in porcine atrium. Immunohistocytochemical study using specific monoclonal antibodies. Circulation 84:1203-1209, 1991[Abstract/Free Full Text]
  17. Hystad ME, Geiran OR, Attramadal H, Spurkland A, Vege A, Simonsen S, Hall C: Regional cardiac expression and concentration of natriuretic peptides in patients with severe chronic heart failure. Acta Physiol Scand 171:395-403, 2001[CrossRef][ISI][Medline]
  18. Levin ER, Gardner DG, Samson WK: Natriuretic peptides. N Engl J Med 339:321-328, 1998[Free Full Text]
  19. Luchner A, Muders F, Dietl O, Friedrich E, Blumberg F, Protter AA, Riegger GA, Elsner D: Differential expression of cardiac ANP and BNP in a rabbit model of progressive left ventricular dysfunction. Cardiovasc Res 51:601-607, 2001[Abstract/Free Full Text]
  20. Luchner A, Stevens TL, Borgeson DD, Redfield M, Wei CM, Porter JG, Burnett JC, Jr: Differential atrial and ventricular expression of myocardial BNP during evolution of heart failure. Am J Physiol 274:H1684-H1689, 1998
  21. Mifune H, Richter R, Forssmann WG: Detection of immunoreactive atrial and brain natriuretic peptides in the equine atrium. Anat Embryol (Berl) 192:117-121, 1995[Medline]
  22. Mifune H, Suzuki S, Noda Y, Hayashi Y, Mochizuki K: Fine structure of atrial natriuretic peptide (ANP)-granules in the atrial cardiocytes in the hamster, guinea pig, rabbit, cat and dog. Jikken Dobutsu 41:321-328, 1992[Medline]
  23. Mizuno Y, Yoshimura M, Harada E, Nakayama M, Sakamoto T, Shimasaki Y, Ogawa H, Kugiyama K, Saito Y, Nakao K, Yasue H: Plasma levels of A- and B-type natriuretic peptides in patients with hypertrophic cardiomyopathy or idiopathic dilated cardiomyopathy. Am J Cardiol 86:1036-1040, 2000[CrossRef][ISI][Medline]
  24. Moe GW, Grima EA, Wong NL, Howard RJ, Armstrong PW: Plasma and cardiac tissue atrial and brain natriuretic peptides in experimental heart failure. J Am Coll Cardiol 27:720-727, 1996[Abstract]
  25. Mukoyama M, Nakao K, Hosoda K, Suga S, Saito Y, Ogawa Y, Shirakami G, Jougasaki M, Obata K, Yasue H, Kambayashi Y, Inouye K, Imara H: 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. J Clin Invest 87:1402-1412, 1991
  26. Nakagawa M, Tanaka I, Suga S, Ogawa Y, Tamura N, Goto M, Sugawara A, Yoshimasa T, Itoh H, Mukoyama M, Nakao K: Preparation of a monoclonal antibody against mouse brain natriuretic peptide (BNP) and tissue distribution of BNP in mice. Clin Exp Pharmacol Physiol Suppl 22:S186-S187, 1995[Medline]
  27. Nakamura S, Naruse M, Naruse K, Kawana M, Nishikawa T, Hosoda S, Tanaka I, Yoshimi T, Yoshihara I, Inagami T: Atrial natriuretic peptide and brain natriuretic peptide coexist in the secretory granules of human cardiac myocytes. Am J Hypertens 4:909-912, 1991[ISI][Medline]
  28. Nemer M, Lavigne JP, Drouin J, Thibault G, Gannon M, Antakly T: Expression of atrial natriuretic factor gene in heart ventricular tissue. Peptides 7:1147-1152, 1986[CrossRef][ISI][Medline]
  29. Ogawa Y, Nakao K, Mukoyama M, Hosoda K, Shirakami G, Arai H, Saito Y, Suga S, Jougasaki M, Imura H: Natriuretic peptides as cardiac hormones in normotensive and spontaneously hypertensive rats. The ventricle is a major site of synthesis and secretion of brain natriuretic peptide. Circ Res 69:491-500, 1991[Abstract/Free Full Text]
  30. Raizada V, Thakore K, Luo W, McGuire PG: Cardiac chamber-specific alterations of ANP and BNP expression with advancing age and with systemic hypertension. Mol Cell Biochem 216:137-140, 2001[CrossRef][ISI][Medline]
  31. Rinne A, Vuolteenaho O, Jarvinen M, Dorn A, Arjamaa O: Atrial natriuretic polypeptides in the specific atrial granules of the rat heart: immunohistochemical and immunoelectron microscopical localization and radioimmunological quantification. Acta Histochem 80:19-28, 1986[ISI][Medline]
  32. Takayanagi R, Imada T, Inagami T: Synthesis and presence of atrial natriuretic factor in rat ventricle. Biochem Biophys Res Commun 142:483-488, 1987[CrossRef][ISI][Medline]
  33. Takemura G, Fujiwara H, Mukoyama M, Saito Y, Matsuda M, Kawamura A, Ishida M, Kida M, Uegaito T, Nakao K: Immunohistochemical localization and semi-quantification of atrial natriuretic polypeptide (ANP) in formalin-fixed-paraffin-embedded normal human hearts—comparative study with radioimmunoassay. Jpn Circ J 53:686-694, 1989[Medline]
  34. Takemura G, Fujiwara H, Mukoyama M, Saito Y, Nakao K, Kawamura A, Ishida M, Kida M, Uegaito T, Tanaka M, Matsumori A, Fujiwara T, Imura H, Kawai C: Expression and distribution of atrial natriuretic peptide in human hypertrophic ventricle of hypertensive hearts and hearts with hypertrophic cardiomyopathy. Circulation 83:181-190, 1991[Abstract/Free Full Text]
  35. Takemura G, Fujiwara H, Takatsu Y, Fujiwara T, Nakao K: Ventricular expression of atrial and brain natriuretic peptides in patients with myocarditis. Int J Cardiol 52:213-222, 1995[CrossRef][ISI][Medline]
  36. Takemura G, Takatsu Y, Doyama K, Itoh H, Saito Y, Koshiji M, Ando F, Fujiwara T, Nakao K, Fujiwara H: Expression of atrial and brain natriuretic peptides and their genes in hearts of patients with cardiac amyloidosis. J Am Coll Cardiol 31:754-765, 1998[Abstract/Free Full Text]
  37. Tanaka M, Hiroe M, Nishikawa T, Sato T, Marumo F: Cellular localization and structural characterization of natriuretic peptide-expressing ventricular myocytes from patients with dilated cardiomyopathy. J Histochem Cytochem 42:1207-1214, 1994[Abstract]
  38. Thibault G, Charbonneau C, Bilodeau J, Schiffrin EL, Garcia R: Rat brain natriuretic peptide is localized in atrial granules and released into the circulation. Am J Physiol 263:R301-R309, 1992
  39. Toshimori H, Nakazato M, Toshimori K, Asai J, Matsukura S, Oura C, Matsuo H: Distribution of atrial natriuretic polypeptide (ANP)-containing cells in the rat heart and pulmonary vein. Immunohistochemical study and radioimmunoassay. Cell Tissue Res 251:541-546, 1988[CrossRef][ISI][Medline]
  40. Turk JR: Physiologic and pathophysiologic effects of natriuretic peptides and their implications in cardiopulmonary disease. J Am Vet Med Assoc 216:1970-1976, 2000[CrossRef][ISI][Medline]
  41. Yamada H, Saito Y, Mukoyama M, Nakao K, Yasue H, Ban T, Imura H, Sano Y: Immunohistochemical localization of atrial natriuretic polypeptide (ANP) in human atrial and ventricular myocardiocytes. Histochemistry 89:411-413, 1988[CrossRef][ISI][Medline]
  42. Yamamoto R, McGlinn A, Stone RA: Brain natriuretic peptide-immunoreactive nerves in the porcine eye. Neurosci Lett 122:151-153, 1991[CrossRef][ISI][Medline]
Request reprints from Dr. P. F. Solter, Department of Veterinary Pathobiology, University of Illinois, 2001 South Lincoln Avenue, Urbana, IL 61802 (USA). E-mail: psolter{at}uiuc.edu.





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