NO-donors, part 9 : diazeniumdiolates inhibit human platelet aggregation and induce a transient vasodilatation of porcine pulmonary arteries in accordance with the NO-releasing rates.
Eur J Med Chem
; 40(3): 281-7, 2005 Mar.
Article
em En
| MEDLINE
| ID: mdl-15725497
ABSTRACT
Diazeniumdiolates (NONOates), among them a ciprofloxacin-diazeniumdiolate hybrid compound, were synthesized and the pH-, temperature- and structure-dependent liberation of nitric oxide (NO) was monitored by laser magnetic resonance spectroscopy (LMRS). The compounds induced a transient and reversible relaxation (EC(50) 8.3-150 nM) of pulmonary arteries independently from intact endothelium by stimulation of guanylyl cyclase (sGC). Increase in vascular cGMP was observed and blocking sGC with ODQ, an inhibitor of the NO-sensitive guanylyl cyclase, induced a rightward shift of the concentration-response curves. Repeated exposure did not show homologous desensitization. ADP-induced platelet aggregation (IC(50) = 0.15-3 microM, IC(50) for SNP 2 microM) and collagen-induced aggregation were potently inhibited. Preincubation with ODQ also diminished these inhibitory effects.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
/
Compostos Azo
/
Vasodilatação
/
Endotélio Vascular
/
Inibidores da Agregação Plaquetária
/
Agregação Plaquetária
/
Doadores de Óxido Nítrico
/
Guanilato Ciclase
Limite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Alemanha