Modulation of nitric oxide-dependent vascular and platelet function in-vitro by the novel phosphodiesterase type-V inhibitor, ONO-1505

We have characterized the in-vitro modulation of both nitric oxide (NO)-dep endent vasodilator activity and anti-platelet function by the novel type-V phosphodiesterase inhibitor, ONO-1505 (4-[2-(2-hydroxyethoxy)ethylamino]-2- (1H-imidazol-1-yl)-6-methoxy-quinazoline methanesulphonate). ONO-1505 elicited vasorelaxation in the rat isolated aorta, if the concentr ation of ONO-1505 was less than or equal to 10 mu M the vasorelaxation was abolished by NG-nitro-L-arginine methyl ester (L-NAME), by methylene blue, and by endothelial denudation. Furthermore, pretreatment of the rat isolate d aorta for 10 min with ONO-1505 in the presence of L-NAME potentiated vaso relaxation to the NO-donor, sodium nitroprusside, Similarly, ONO-1505, alth ough having no effect on adenosine diphosphate (ADP)-induced rat platelet a ggregation in-vitro, augmented established anti-aggregatory effects of sodi um nitroprusside. The data therefore show that the novel phosphodiesterase V inhibitor ONO-15 05 augments endogenous and exogenous nitrovasodilator activity in-vitro; th ey also imply modulation of the NO pathway in the haemodynamic actions of t his compound, previously reported in-vivo.