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Journal of Histochemistry and Cytochemistry, Vol. 49, 1293-1300, October 2001, Copyright © 2001, The Histochemical Society, Inc.

ARTICLE

Evaluation of Atrial Natriuretic Peptide and Brain Natriuretic Peptide in Atrial Granules of Rats with Experimental Congestive Heart Failure

Gad M. Bialika, Zaid A. Abassib, Ilan Hammelc, Joseph Winaverb, and Dina Lewinsona
a Departments of Anatomy and Cell Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
b Physiology and Biophysics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
c The Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, and the Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Correspondence to: Dina Lewinson, Dept. of Anatomy and Cell Biology, The Bruce Rappaport Faculty of Medicine, Technion–Israel Inst. of Technology, POB 9649, 31096 Haifa, Israel. E-mail: dinal@tx.technion.ac.il

The natriuretic peptides are believed to play an important role in the pathophysiology of congestive heart failure (CHF). We utilized a quantitative cytomorphometric method, using double immunocytochemical labeling, to assess the characteristics of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in atrial granules in an experimental model of rats with CHF induced by aortocaval fistula. Rats with CHF were further divided into decompensated (sodium-retaining) and compensated (sodium-excreting) subgroups and compared with a sham-operated control group. A total of 947 granules in myocytes in the right atrium were analyzed, using electron microscopy and a computerized analysis system. Decompensated CHF was associated with alterations in the modal nature of granule content packing, as depicted by moving bin analysis, and in the granule density of both peptides. In control rats, the mean density of gold particles attached to both peptides was 347.0 ± 103.6 and 306.3 ± 89.9 gold particles/µm2 for ANP and BNP, respectively. Similar mean density was revealed in the compensated rats (390.6 ± 81.0 and 351.3 ± 62.1 gold particles/µm2 for ANP and BNP, respectively). However, in rats with decompensated CHF, a significant decrease in the mean density of gold particles was observed (141.6 ± 67.3 and 158.0 ± 71.2 gold particles/µm2 for ANP and BNP, respectively; p<0.05 compared with compensated rats, for both ANP and BNP). The ANP:BNP ratio did not differ between groups. These findings indicate that the development of decompensated CHF in rats with aortocaval fistula is associated with a marked decrease in the density of both peptides in atrial granules, as well as in alterations in the quantal nature of granule formation. The data further suggest that both peptides, ANP and BNP, may be regulated in the atrium by a common secretory mechanism in CHF. (J Histochem Cytochem 49:1293–1300, 2001)

Key Words: ANP, BNP, heart failure, immunocytochemistry, quantitative microscopy, atrium, rat


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