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Cardiac and plasma atrial natriuretic factor in experimental congestive heart failure
Insights
Congestive heart failure in hamsters increases plasma immunoreactive atrial natriuretic factor (ANF) and ventricular ANF, while decreasing atrial ANF. This suggests hypersecretion from both atrial and ventricular cells contributes to elevated ANF levels during heart failure.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Cell Biology
Background:
- Atrial natriuretic factor (ANF) plays a crucial role in cardiovascular homeostasis.
- Congestive heart failure (CHF) is associated with altered ANF levels, but the cellular mechanisms remain unclear.
- Cardiomyopathic hamsters serve as a model to study heart failure progression and its endocrine consequences.
Purpose of the Study:
- To investigate cardiac and plasma levels of immunoreactive ANF (IR-ANF) in hamsters with varying degrees of CHF.
- To correlate IR-ANF levels with cellular ultrastructure and molecular forms (HPLC) in heart tissue and plasma.
- To elucidate the cellular source and mechanisms of increased IR-ANF in CHF.
Main Methods:
- Measurement of IR-ANF in atria, ventricles, and plasma of control and cardiomyopathic hamsters.
- High-performance liquid chromatography (HPLC) analysis to characterize molecular forms of IR-ANF.
- Electron microscopy and immunocytochemistry (immunogold technique) to examine atrial and ventricular cardiocyte ultrastructure and ANF localization.
Main Results:
- CHF significantly increased plasma IR-ANF and ventricular IR-ANF, while decreasing atrial IR-ANF.
- High molecular weight forms of ANF appeared in plasma of severe CHF hamsters.
- Severe CHF led to increased Golgi complex size and reduced secretory granules in atrial cells, and increased secretory granules containing IR-ANF in ventricular cells.
Conclusions:
- Increased plasma and ventricular IR-ANF in CHF hamsters likely results from hypersecretion by both atrial and ventricular cardiocytes.
- The presence of IR-ANF in ventricular secretory granules suggests a novel role for ventricular cardiomyocytes in ANF production during heart failure.
- Alterations in cardiocyte ultrastructure, particularly the Golgi complex and secretory granules, support enhanced ANF synthesis and release in CHF.
Abstract:
The cardiac and plasma levels of immunoreactive (IR-) atrial natriuretic factor (ANF) in cardiomyopathic hamsters with moderate and severe congestive heart failure were measured, compared with those of controls, and correlated by HPLC analysis of IR-ANF in atria, ventricles, and plasma and with the ultrastructure of atrial and ventricular cells. Congestive heart failure in the hamster produced a significant increase in plasma IR-ANF, a significant decrease in atrial IR-ANF, and a marked increase in ventricular IR-ANF. The HPLC pattern of IR-ANF was of the high mol wt type in atria and ventricles of control and cardiomyopathic animals. High mol wt forms of ANF appeared in the plasma of animals with severe congestive heart failure, but not in controls. Severe congestive heart failure produced a tremendous increase in the size of the Golgi complex, with a decrease in the number and size of secretory granules in atrial cardiocytes. Ventricular cardiocytes also showed a less marked increase in the size of the Golgi complex. Secretory-like granules indistinguishable from lysosomes were present in about 1% of ventricular cardiocytes of control hamsters; in hamsters with severe congestive heart failure, secretory granules, identical to those of atrial cardiocytes, were present in greater number in about 20% of ventricular cardiocytes. Immunocytochemistry (immunogold technique) revealed that secretory granules containing IR-ANF are not present in control ventricular cardiocytes but are localized in relatively large number in about 20% of ventricular cardiocytes in hamsters with severe congestive heart failure. These results suggest that the increased IR-ANF levels (including the high mol wt forms) in animals with congestive heart failure may come from hypersecretion of both atrial and ventricular cardiocytes.