Document Detail

Role of myocyte nitric oxide in beta-adrenergic hyporesponsiveness in heart failure.
MedLine Citation:
PMID:  9054836     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The positive inotropic response to beta-adrenergic stimulation is attenuated at the isolated myocyte level in heart failure. Nitric oxide (NO) has a negative inotropic effect and attenuates the response to isoproterenol. It has been suggested that NO synthesis is increased in failing myocytes. However, the pathophysiological consequences after induction of NO in myocyte contractility are less clear in the setting of heart failure. METHODS AND RESULTS: We examined the effects of an NO synthase (NOS) inhibitor on contractile function in myocytes isolated from 11 dogs with rapid pacing-induced heart failure (ejection fraction, 29 +/- 2%) and 8 control dogs (ejection fraction, 74 +/- 3%). Sarcomere shortening velocity was measured as an index of contractility under four experimental conditions: at baseline, after adding isoproterenol (ISO; 1 nmol/L), after an NOS inhibitor (N pi-nitro-L-arginine methyl ester [L-NAME], 0.1 nmol/L), and after L-NAME plus ISO. L-NAME alone had no effects on basal sarcomere shortening velocity in either control or heart failure myocytes. However, L-NAME significantly augmented the inotropic response to isoproterenol in heart failure myocytes (107.1 +/- 7.3% [ISO alone] versus 140.6 +/- 10.7% [ISO plus L-NAME] increase from baseline; P < .05) but not in control myocytes (135.5 +/- 9.9% [ISO alone] versus 137.1 +/- 11.4% [ISO plus L-NAME]; P = NS). Myocardial NOS activity measured by the conversion of arginine to citrulline was significantly increased in dogs with heart failure compared with that in control dogs. CONCLUSIONS: The increased NO induction in failing myocytes does not alter baseline sarcomere mechanics but attenuates the positive inotropic response to isoproterenol. Thus, myocyte NO plays an important role in the autocrine regulation of the contractile function of myocytes in congestive heart failure.
S Yamamoto; H Tsutsui; H Tagawa; K Saito; M Takahashi; H Tada; M Yamamoto; M Katoh; K Egashira; A Takeshita
Related Documents :
23103036 - Effects of radial versus femoral artery access in patients with acute coronary syndrome...
24489126 - Acute seizures in the acute ischemic stroke setting: a step forward in their description.
19951746 - Thyroid hormone as a therapeutic option for treating ischaemic heart disease: from earl...
12715086 - Inotropic effects of extracts of psidium guajava l. (guava) leaves on the guinea pig at...
16195616 - Angiographic and clinical outcomes of a pharmacokinetic study of sirolimus-eluting sten...
6856526 - Missed large left ventricular thrombus. failure of two-dimensional echocardiography in ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  95     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-03-28     Completed Date:  1997-03-28     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1111-4     Citation Subset:  AIM; IM    
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adrenergic beta-Agonists / pharmacology*
Analysis of Variance
Cells, Cultured
Electric Stimulation
Heart / drug effects*,  physiology,  physiopathology
Heart Failure / physiopathology*
Isoproterenol / pharmacology*
Myocardial Contraction / drug effects*
Myocardium / metabolism
NG-Nitroarginine Methyl Ester / pharmacology*
Nitric Oxide / physiology*
Nitric Oxide Synthase / antagonists & inhibitors,  metabolism*
Sarcomeres / drug effects,  physiology
Ventricular Function, Left / drug effects
Reg. No./Substance:
0/Adrenergic beta-Agonists; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 7683-59-2/Isoproterenol; EC Oxide Synthase

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

Previous Document:  Toronto centre hopes to cash in on growing demand for private health services.
Next Document:  Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in huma...