Document Detail


Generation of NO from molsidomine (SIN-1) in vitro and its relationship to changes in coronary vessel tone.
MedLine Citation:
PMID:  2484696     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The release of NO from SIN-1, the active metabolite of molsidomine, was measured in vitro in Langendorff-perfused rabbit hearts. NO in the coronary effluent was determined on-line using the oxyhemoglobin technique. Left ventricular and coronary perfusion pressure were also recorded continuously. Glyceryl trinitrate and iloprost were used as reference compounds. Infusion of SIN-1 or glyceryl trinitrate into the coronary inflow resulted in a significant and dose-dependent NO release. An apparently identical response was seen when SIN-1 was infused into the coronary effluent while the response to glyceryl trinitrate was greatly reduced or abolished. The glyceryl trinitrate-induced coronary vasodilation was only slightly diminished in presence of oxyhemoglobin whereas the response to SIN-1 was abolished. This is explained by complete scavenging of NO by oxyhemoglobin within the vessel lumen. In isolated porcine aortic endothelial cells, SIN-1 induced a significant and dose-dependent increase in cyclic GMP, whereas glyceryl trinitrate was ineffective. This would argue against biotransformation of glyceryl trinitrate to NO by endothelial cells. Finally, glyceryl trinitrate-tolerant heart preparations exhibited a considerably reduced or even undetectable release of NO, whereas the response to SIN-1 was unchanged.
Authors:
K Schrör; S Förster; I Woditsch; H Schröder
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  14 Suppl 11     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1989  
Date Detail:
Created Date:  1990-12-27     Completed Date:  1990-12-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  S29-34     Citation Subset:  IM    
Affiliation:
Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, F.R.G.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Coronary Circulation / drug effects
Coronary Vessels / drug effects*
Cyclic GMP / metabolism
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects
Enzyme Activation / drug effects
Iloprost / pharmacology
Molsidomine / analogs & derivatives*,  pharmacokinetics,  pharmacology
Nitric Oxide / pharmacokinetics*
Nitroglycerin / pharmacology
Oxyhemoglobins / metabolism
Rabbits
Vasodilator Agents / pharmacokinetics*,  pharmacology
Chemical
Reg. No./Substance:
0/Oxyhemoglobins; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 25717-80-0/Molsidomine; 33876-97-0/3-morpholino-sydnonimine; 55-63-0/Nitroglycerin; 7665-99-8/Cyclic GMP; 78919-13-8/Iloprost

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


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