Endothelium‐independent relaxation of aortic rings by the nitric oxide synthase inhibitor diphenyleneiodonium

摘要: The flavoprotein binder diphenyleneiodonium (DPI) is a potent, irreversible inhibitor of nitric oxide synthase (NOS), but produces only transient pressor response following systemic administration to animals, despite evidence persistent NOS inhibition. To characterize further the effects DPI on vascular tone, isometric tension was recorded from rat isolated aortic rings mounted between steel wires in an organ bath. The NG-nitro-l-arginine methyl ester (l-NAME, 1 mm) initiated additional contraction prostaglandin F2α-preconstricted with endothelium which sustained throughout period l-NAME exposure (+234±39% at 15 min). In contrast, addition (5 μm) produced initial (+111±27% 2 min) followed by more relaxation (−27±19% min, P<0.001 vs l-NAME). The also observed without endothelium, abolished pretreatment, and unaffected α-adrenoreceptor prazosin. Relaxation not inhibited removal or pretreatment either ATP-sensitive potassium channel blocker glibenclamide. The endothelium-independent 23°C its time course delayed guanylate cyclase methylene blue. Thus, due inhibition, endothelium-independent, temperature-dependent appears part activation cyclase. This relaxant effect may explain nature vivo inhibition. British Journal Pharmacology (1997) 120, 857–864; doi:10.1038/sj.bjp.0701014