Document Detail


Chronic nitric oxide synthase blockade desensitizes the heart to the negative metabolic effects of nitric oxide.
MedLine Citation:
PMID:  16831448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The consequences of chronic nitric oxide synthase (NOS) blockade on the myocardial metabolic and guanylyl cyclase stimulatory effects of exogenous nitric oxide (NO) were determined. Thirty-three anesthetized open-chest rabbits were randomized into four groups: control, NO donor S-nitroso-N-acetyl-penicillamine (SNAP, 10(-4 )M), NOS blocking agent N(G)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg/day) for 10 days followed by a 24 hour washout and L-NAME for 10 days followed by a 24 hour washout plus SNAP. Myocardial O(2) consumption was determined from coronary flow (microspheres) and O(2) extraction (microspectrophotometry). Cyclic GMP and guanylyl cyclase activity were determined by radioimmunoassay. There were no baseline metabolic, functional or hemodynamic differences between control and L-NAME treated rabbits. SNAP in controls caused a reduction in O(2) consumption (SNAP 5.9+/-0.6 vs. control 8.4+/-0.8 ml O(2)/min/100 g) and a rise in cyclic GMP (SNAP 18.3+/-3.8 vs. control 10.4+/-0.9 pmol/g). After chronic L-NAME treatment, SNAP caused no significant changes in O(2) consumption (SNAP 7.1+/-0.8 vs. control 6.4+/-0.7) or cyclic GMP (SNAP 14.2+/-1.8 vs. control 12.1+/-1.3). In controls, guanylyl cyclase activity was significantly stimulated by SNAP (216.7+/-20.0 SNAP vs. 34.4+/-2.5 pmol/mg/min base), while this increase was blunted after L-NAME (115.9+/-24.5 SNAP vs. 24.9+/-4.7 base). These results demonstrated that chronic NOS blockade followed by washout blunts the response to exogenous NO, with little effect on cyclic GMP or myocardial O(2) consumption. This was related to reduced guanylyl cyclase activity after chronic L-NAME. These results suggest that, unlike many receptor systems, the NO-cyclic GMP signal transduction system becomes downregulated upon chronic inhibition.
Authors:
Tomer Davidov; Harvey R Weiss; James Tse; Peter M Scholz
Related Documents :
1310588 - Intravitreal sustained-release ganciclovir.
22627678 - Phase ib study of the flt3 kinase inhibitor midostaurin with chemotherapy in younger ne...
453588 - Steriod therapy for pneumonitis induced in rabbits by aspiration of foodstuff.
21121368 - Dose dependent in vivo metabolic characteristics of titanium dioxide nanoparticles.
3288768 - Effect of induced synovial inflammation on pharmacokinetics and synovial concentration ...
2834178 - Chronic exposure of the developing corpus luteum in monkeys to chorionic gonadotropin: ...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-06-08
Journal Detail:
Title:  Life sciences     Volume:  79     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-18     Completed Date:  2006-11-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1674-80     Citation Subset:  IM    
Affiliation:
Heart and Brain Circulation Laboratory, Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Blood Flow Velocity / drug effects
Cyclic GMP / metabolism*
Enzyme Inhibitors / pharmacology
Female
Guanylate Cyclase / metabolism
Heart / drug effects,  physiology*
Heart Ventricles / chemistry,  drug effects,  metabolism
Hemodynamics / drug effects
Male
Microspectrophotometry
Microspheres
Myocardium / metabolism*
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / metabolism*
Nitric Oxide Donors / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors*
Oxygen / analysis
Oxygen Consumption / drug effects,  physiology*
Penicillamine / analogs & derivatives,  pharmacology
Rabbits
Grant Support
ID/Acronym/Agency:
HL 40320/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Nitric Oxide Donors; 0/S-nitro-N-acetylpenicillamine; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 52-67-5/Penicillamine; 7665-99-8/Cyclic GMP; 7782-44-7/Oxygen; EC 1.14.13.39/Nitric Oxide Synthase; EC 4.6.1.2/Guanylate Cyclase

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


Previous Document:  Stress and HPA-axis functioning in young people at ultra high risk for psychosis.
Next Document:  Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid prof...