Document Detail

In vitro comparison of two NONOates (novel nitric oxide donors) on rat pulmonary arteries.
MedLine Citation:
PMID:  9761423     Owner:  NLM     Status:  MEDLINE    
The pulmonary vasorelaxant properties of two NONOates (diazeniumdiolates) were examined because this novel group of nitric oxide (NO) donors may be useful in pulmonary hypertension. MAHMA NONOate ((Z)-1-¿N-Methyl-N-[6-(N-methylammoniohexyl)amino]¿ diazen-1-ium-1,2-diolate) and spermine NONOate ((Z)- 1-¿N-[3-aminopropyl]-N-[4-(3-aminopropylammonio)butyl]-amino¿di azen-1-ium-1,2-diolate) decomposed at different rates (half-lives 1.3 min and 73 min, respectively; 37 degrees C, pH 7.3) but generated the same total amount of NO. They fully relaxed submaximally contracted ring preparations of main and intralobar pulmonary arteries from rats. Responses were inhibited by the guanylate cyclase inhibitor, ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one). Potency was not affected by choice of contractile spasmogen (phenylephrine, endothelin-1, thromboxane-mimetic) or endothelium removal, and tolerance did not develop; thus the drugs had properties important for use in pulmonary hypertension. MAHMA NONOate was 10-40-fold more potent than spermine NONOate but responses to spermine NONOate were more sustained (spermine NONOate > 60 min; MAHMA NONOate < 7 min). It is concluded that the differences in potency and time-course reflect the different rates of NO generation by these NONOates.
K Homer; J Wanstall
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  356     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-12-14     Completed Date:  1998-12-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  49-57     Citation Subset:  IM    
Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Australia.
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MeSH Terms
Dose-Response Relationship, Drug
Drug Tolerance
Enzyme Inhibitors / pharmacology
Guanylate Cyclase / antagonists & inhibitors
Hydrazines / chemistry,  metabolism,  pharmacology*
Mutagens / chemistry,  metabolism,  pharmacology*
Nitric Oxide / metabolism
Nitrogen Oxides
Nitroglycerin / pharmacology
Oxadiazoles / pharmacology
Pulmonary Artery / drug effects*,  physiology
Quinoxalines / pharmacology
Rats, Wistar
Spermine / analogs & derivatives*,  chemistry,  metabolism,  pharmacology
Vasodilation / drug effects
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl; 0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/Enzyme Inhibitors; 0/Hydrazines; 0/Mutagens; 0/Nitrogen Oxides; 0/Oxadiazoles; 0/Quinoxalines; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 136587-13-8/spermine nitric oxide complex; 55-63-0/Nitroglycerin; 71-44-3/Spermine; EC Cyclase

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