Document Detail


Reduced endothelium-dependent relaxation at enhanced NO release in hearts of hypercholesterolaemic rabbits.
MedLine Citation:
PMID:  8032587     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Langendorff hearts, perfused at constant volume, were prepared from rabbits fed a cholesterol-enriched diet for 4 months. Coronary perfusion pressure and nitric oxide (NO) release (oxyhaemoglobin technique) into the coronary effluent were measured continuously. Prostacyclin (PGI2) in the effluents was determined by radioimmunoassay (6-oxo-PGF1 alpha). 2. Basal NO release was not different between control and hypercholesterolaemic rabbits. However, the coronary vasculature of hypercholesterolaemic rabbits showed a considerably (> 50%) reduced endothelium-dependent relaxation in response to short-term (3 min) infusion of bradykinin (50 nM) and substance P (50 nM) (P < 0.05, n = 8-9). Under these conditions, NO release into the vessel lumen was increased, by 26%, in hypercholesterolaemic hearts (P < 0.05, n = 8-9). NG-nitro-L-arginine (L-NOARG, 30 microM) significantly attenuated both bradykinin-induced NO formation and vessel relaxation in control hearts but only NO release in hypercholesterolaemia. L-Arginine (200 microM) restored the response to that before L-NOARG but did not improve the reduced endothelium-dependent relaxation in cholesterol-fed rabbits. 3. Superoxide dismutase (10 u ml-1) significantly improved vessel relaxation without changing the hypercholesterolaemia-related coronary dysfunction. Vasodilatation in response to exogenous NO donors (linsidomine) was diminished in hypercholesterolaemia as compared to controls. 4. Basal PGI2 release was unchanged in hypercholesterolaemic hearts. There was a tendency in these hearts for greater PGI2 formation after stimulation by substance P and bradykinin (P > or = 0.05). The coronary relaxation to iloprost was unchanged. 5. The data demonstrate impaired endothelium-dependent relaxation of coronary arterial resistance vessels in hypercholesterolaemia. This diminished vascular response was not due to reduced NO generation but probably a reduced action of released NO, either by accelerated degradation and/or disturbed signal transduction pathways to vascular smooth muscle cells. There was no significant change in PGI2 related pathways of vasomotor control in hypercholesterolaemia.
Authors:
I Woditsch; K Schrör
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  111     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-08-17     Completed Date:  1994-08-17     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1035-40     Citation Subset:  IM    
Affiliation:
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginine / analogs & derivatives,  pharmacology
Coronary Vessels / physiopathology*
Endothelium, Vascular / physiology*
Epoprostenol / biosynthesis
Hypercholesterolemia / physiopathology*
Myocardium / metabolism*
Nitric Oxide / metabolism*
Nitroarginine
Rabbits
Superoxide Dismutase / pharmacology
Vasodilation*
Chemical
Reg. No./Substance:
10102-43-9/Nitric Oxide; 2149-70-4/Nitroarginine; 35121-78-9/Epoprostenol; 74-79-3/Arginine; EC 1.15.1.1/Superoxide Dismutase
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