Document Detail

Developmental pattern of ventricular atrial natriuretic peptide (ANP) expression in chronically hypoxic rats as an indicator of the hypertrophic process.
MedLine Citation:
PMID:  8089855     Owner:  NLM     Status:  MEDLINE    
Atrial natriuretic peptide (ANP) is a natriuretic, diuretic and vasodilatory peptide normally synthesized and secreted by the atria of the adult mammalian heart. Synthesis of ANP in the ventricle has also been demonstrated in the fetus and neonate. In the adult, ventricular ANP is expressed under pathological conditions such as hypertension and congestive heart failure. The purpose of the present study was to analyse the spatial and temporal development of ANP expression in the right ventricle of the rat heart during the onset, establishment, and recovery from hypoxia-induced pulmonary hypertension and right ventricular hypertrophy (RVH). Significant RVH and immunoreactive ANP (ir-ANP) were detected in the right ventricles of hypoxic rats after only 3 days of exposure and continued to increase with the duration of hypoxia through 21 days. The presence of ir-ANP became apparent in the left ventricle as well as the right after 14 days of hypoxic exposure. Twenty-one days of normoxia following 21 days of hypoxia reduced RVH and ir-ANP to the levels seen at 3 days. Light microscopic immunohistochemistry demonstrated initial focal concentrations of ir-ANP in cardiomyocytes near the junction of the right ventricular free wall and the septum, as well as surrounding isolated blood vessels in the right ventricular wall, after 3 days of exposure. With increasing duration of hypoxic exposure, these immunoreactive areas enlarged to encompass the entire right ventricular wall and right half of the septum by 14 days. While many right ventricular cardiomyocytes were intensely stained at the light level, electron microscopic immunocytochemistry revealed only a sparse number of ANP-positive secretory granules. In immunohistochemical studies with an anti-clathrin antibody, there was a homogeneous staining pattern for clathrin in cardiomyocytes from the hypertrophied right ventricles. This pattern was not typical of the staining observed in other secretory cells which typically exhibit a perinuclear localization of clathrin. The alterations in ultrastructural immunocytochemistry for ANP suggest that ventricular ANP synthesis differs from atrial synthesis of this peptide. The differences in clathrin staining indicate that its expression may also be related to the hypertrophic adaptation of ventricular cardiomyocytes. Our results suggest that ventricular ANP expression in the adult rat is a dynamic event which is regulated by stress in the ventricular wall. The initial sites of ventricular ANP expression may represent zones of maximum tension in the ventricular wall following increased workload. To our knowledge this is the first study to demonstrate topographical changes in ventricular ANP expression in response to the development and reversal of cardiac hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)
J C McKenzie; K B Kelley; E M Merisko-Liversidge; J Kennedy; R M Klein
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  26     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-10-18     Completed Date:  1994-10-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  753-67     Citation Subset:  IM    
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160-7400.
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MeSH Terms
Amino Acid Sequence
Anoxia / complications*
Atrial Natriuretic Factor / biosynthesis*
Biological Markers
Clathrin / biosynthesis
Hypertension, Pulmonary / complications,  metabolism*,  pathology
Hypertrophy, Right Ventricular / complications,  metabolism*,  pathology
Molecular Sequence Data
Myocardium / metabolism*,  pathology,  ultrastructure
Rats, Sprague-Dawley
Grant Support
R29 HL 45241-01/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Biological Markers; 0/Clathrin; 85637-73-6/Atrial Natriuretic Factor

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