Document Detail


An inhibitor of nitric oxide synthase does not increase contraction or beta-adrenoceptor sensitivity of ventricular myocytes from failing human heart.
MedLine Citation:
PMID:  10070493     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Nitric oxide (NO) has been implicated in the depression of cardiac function in human heart failure. Some reports have identified iNOS (inducible nitric oxide synthase) within the myocyte component of the failing human heart, and NO is known to decrease the contraction amplitude of isolated ventricular myocytes. We have treated myocytes from failing human ventricle with a NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA), in an attempt to restore contractile function. METHODS AND RESULTS: Myocytes were isolated from failing and non-failing human ventricles and their contraction amplitude was measured during superfusion (32 degrees C, 1-2 mmol/l Ca2+) and electrical stimulation (0.1-2 Hz). The contraction amplitude of myocytes from failing hearts was depressed in a frequency-dependent manner. At 1 Hz, the contraction amplitude of cells from non-failing heart was 4.70 +/- 0.53% cell shortening (mean +/- SEM, n = 13 subjects), compared with 2.18 +/- 0.27% (P < 0.01, 11 patients) from patients with ischaemic heart disease (IHD) or 2.56 +/- 0.74% (P < 0.02, six patients) with dilated cardiomyopathy (DCM). Superfusion with 0.1 mmol/l L-NMMA did not increase contraction amplitude in myocytes from failing heart at either 0.2 Hz (n = 11) or 1 Hz (n = 7). Responses to beta-adrenoceptor stimulation were reduced in myocytes from failing human heart, with contraction amplitude in maximum isoprenaline 0.47 +/- 0.11 of that in high Ca2+ in the same cell (n = 6), compared to 0.99 +/- 0.07 in non-failing heart (n = 14, P < 0.01). The presence of 0.1 mmol/l L-NMMA did not increase the isoprenaline/Ca2+ ratio in myocytes from failing heart (0.40 +/- 0.09, P = NS). CONCLUSION: These results do not suggest a functional role for tonic NO production in the frequency-dependent depression of contraction or beta-adrenoceptor desensitisation in myocytes from failing human ventricle.
Authors:
S E Harding; C H Davies; A M Money-Kyrle; P A Poole-Wilson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  40     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1999-04-07     Completed Date:  1999-04-07     Revised Date:  2009-09-29    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  523-9     Citation Subset:  IM    
Affiliation:
Imperial College School of Medicine, National Heart and Lung Institute, London, UK. sian.harding@ic.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Agonists / pharmacology
Adult
Aged
Analysis of Variance
Cell Size / drug effects
Cells, Cultured
Child
Dose-Response Relationship, Drug
Electric Stimulation
Female
Heart Diseases / metabolism*
Humans
Isoproterenol / pharmacology
Male
Middle Aged
Myocardial Contraction / drug effects*
Myocardium / metabolism*
Nitric Oxide Synthase / antagonists & inhibitors*
Receptors, Adrenergic, beta / metabolism*
omega-N-Methylarginine / pharmacology*
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Receptors, Adrenergic, beta; 17035-90-4/omega-N-Methylarginine; 7683-59-2/Isoproterenol; EC 1.14.13.39/Nitric Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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