Document Detail


Mechanisms of atrial and brain natriuretic peptide release from rat ventricular myocardium: effect of stretching.
MedLine Citation:
PMID:  8477647     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ventricular hypertrophy is characterized by augmentation of the synthesis and storage of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). To evaluate in vitro the cellular mechanisms of immunoreactive ANP (IR-ANP) and BNP (IR-BNP) release from ventricular cardiocytes, we measured the secretory response to graded passive myocardial stretch in isolated atrialectomized perfused hypertrophied hearts of 14- to 18-month-old spontaneously hypertensive rats. At this age, the ventricular levels of both IR-ANP and IR-BNP were markedly higher in spontaneously hypertensive (182 +/- 27 and 32 +/- 3 pmol/ventricle, respectively) than in age-matched normotensive Wistar-Kyoto rats (35 +/- 4 and 12 +/- 1 pmol/ventricle, respectively; P < 0.001), whereas the differences between the strains in atrial levels of these peptides were small. The release of natriuretic peptides from ventricles in response to stretch was examined by increasing the volume of the intraventricular balloon for 10 min. Stretching of the hypertrophied ventricles produced a rapid transient (from 1-5 min) increase in both IR-ANP and IR-BNP secretion. As left ventricular pressure rose from 0 to 26 +/- 1 mm Hg, IR-ANP and IR-BNP release into the perfusion fluid increased 1.8 +/- 0.4- and 2.5 +/- 0.2-fold, respectively. Infusion of staurosporine, known to inhibit protein kinase-C activity in heart cells, blocked the stretch-induced increase in IR-ANP release (F = 3.10; P < 0.001, by analysis of variance), but had no effect on basal ventricular IR-ANP secretion (F = 0.87; P = NS). An L-type calcium channel antagonist, diltiazem, had no significant effect on basal (F = 1.20; P = NS) or stretch-stimulated (F = 1.47; P = NS) IR-ANP release from hypertrophied rat myocardium. Chromatographical analysis revealed that the ventricles primarily release the active processed 28- and 45- amino acid ANP- and BNP-like peptides, respectively, both before and during stretch. This study indicates that stretch stimulates both ANP and BNP secretion from hypertropic ventricular myocytes. The results further suggest that protein kinase-C may be involved in stretch-induced ventricular ANP release, whereas the influx of extracellular calcium may not be necessary.
Authors:
P Kinnunen; O Vuolteenaho; H Ruskoaho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  132     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1993 May 
Date Detail:
Created Date:  1993-05-25     Completed Date:  1993-05-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1961-70     Citation Subset:  AIM; IM    
Affiliation:
Department of Pharmacology and Toxicology, University of Oulu, Finland.
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MeSH Terms
Descriptor/Qualifier:
Alkaloids / pharmacology
Animals
Atrial Natriuretic Factor / secretion*
Biomechanics
Chromatography, High Pressure Liquid
Heart / physiopathology*
Heart Ventricles / physiopathology
Hemodynamics
Hypertension / physiopathology
Kinetics
Male
Natriuretic Peptide, Brain
Nerve Tissue Proteins / secretion*
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Staurosporine
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Nerve Tissue Proteins; 114471-18-0/Natriuretic Peptide, Brain; 62996-74-1/Staurosporine; 85637-73-6/Atrial Natriuretic Factor

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