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dc.contributor.authorMartelli, A
dc.contributor.authorTestai, L
dc.contributor.authorAnzini, M
dc.contributor.authorCappelli, A
dc.contributor.authorDi Capua, A
dc.contributor.authorBiava, M
dc.contributor.authorPoce, G
dc.contributor.authorConsalvi, S
dc.contributor.authorGiordani, A
dc.contributor.authorCaselli, G
dc.contributor.authorRovati, L
dc.contributor.authorGhelardini, C
dc.contributor.authorPatrignani, P
dc.contributor.authorSautebin, L
dc.contributor.authorBreschi, MC
dc.contributor.authorCalderone, V
dc.description.abstractSelective cyclooxygenase 2 (COX2) inhibitors (COXIBs) are effective anti-inflammatory and analgesic drugs with improved gastrointestinal (GI) safety compared to nonselective nonsteroidal anti-inflammatory drugs known as traditional (tNSAIDs). However, their use is associated with a cardiovascular (CV) hazard (i.e. increased incidence of thrombotic events and hypertension) due to the inhibition of COX2-dependent vascular prostacyclin. Aiming to design COX2-selective inhibitors with improved CV safety, new NO-releasing COXIBs (NO-COXIBs) have been developed. In these hybrid drugs, the NO-mediated CV effects are expected to compensate for the COXIB-mediated inhibition of prostacyclin. This study evaluates the potential CV beneficial effects of VA694, a promising NO-COXIB, the anti-inflammatory effects of which have been previously characterized in several in vitro and in vivo experimental models. When incubated in hepatic homogenate, VA694 acted as a slow NO-donor. Moreover, it caused NO-mediated relaxant effects in the vascular smooth muscle. The chronic oral administration of VA694 to young spontaneously hypertensive rats (SHRs) significantly slowed down the age-related development of hypertension and was associated with increased plasma levels of nitrates, stable end-metabolites of NO. Furthermore, a significant improvement of coronary flow and a significant reduction of endothelial dysfunction were observed in SHRs submitted to chronic administration of VA694. In conclusion, VA694 is a promising COX2-inhibiting hybrid drug, showing NO releasing properties which may mitigate the CV deleterious effects associated with the COX2-inhibition.
dc.publisherAcademic Press
dc.relation.ispartofjournalPharmacological Research
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences not elsewhere classified
dc.titleThe novel anti-inflammatory agent VA694, endowed with both NO-releasing and COX2-selective inhibiting properties, exhibits NO-mediated positive effects on blood pressure, coronary flow and endothelium in an experimental model of hypertension and endothelial dysfunction
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorDi Capua, Angela

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