Document Detail

Mechanical transduction of nitric oxide synthesis in the beating heart.
MedLine Citation:
PMID:  9285639     Owner:  NLM     Status:  MEDLINE    
NO alters contractile and relaxant properties of the heart. However, it is not known whether changes in ventricular loading conditions affect cardiac NO synthesis. To understand this potential contractile-relaxant autoregulatory mechanism, production of cardiac NO in response to mechanical stimuli was measured in vivo using a porphyrinic sensor placed in the left ventricular myocardium. The beating rabbit heart exhibited cyclic changes in [NO], peaking at 2.7+/-0.1 micromol/L near the endocardium and 0.93+/-0.20 micromol/L in the midventricular myocardium (concentrations were 15+/-4% lower in the rat heart). In the present study, we demonstrate for the first time that increasing or decreasing ventricular preload in vivo is followed by parallel changes in [NO], which may represent a novel autoregulatory mechanism to adjust cardiac performance or perfusion on a beat-to-beat basis. To quantify the relationship between applied force and NO synthesis, intermittent compressive or distending forces applied to ex vivo nonbeating hearts were shown to cause bursts of NO synthesis, with peak [NO] linearly related to ventricular transmural pressure. Experiments in which denuding cardiac endothelial and endocardial cells abrogated the NO signal indicate that these cells transduce mechanical stimulation into NO production in the heart. Taken together, these studies may help explain load-dependent relaxation, cardiac memory for mechanical events of preceding beats, diseases associated with myocardial distension, autoregulation of myocardial perfusion, and protection from thrombosis in the turbulent flow environment within the beating heart.
D J Pinsky; S Patton; S Mesaros; V Brovkovych; E Kubaszewski; S Grunfeld; T Malinski
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  81     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-09-25     Completed Date:  1997-09-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  372-9     Citation Subset:  IM; S    
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
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MeSH Terms
Calcium / metabolism
Endocardium / metabolism
Heart / physiology
Myocardial Contraction / physiology*
Myocardium / metabolism*
Nitric Oxide / biosynthesis*
Rats, Inbred WKY
Stress, Mechanical
Grant Support
Reg. No./Substance:
10102-43-9/Nitric Oxide; 7440-70-2/Calcium

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