Effects of a Selective Inhibitor of Inducible Nitric Oxide Synthase, ONO-1714, on Experimental Hemodialysis-Related Hypotension in Renal Dysfunctional Dogs

• Published in: Journal of Pharmacological Sciences 2004, Vol.96(3), pp.343-346
• Main Authors: Komeno, Masaharu, Akimoto, Akira, Fujita, Tsuneo, Katsube, Nobuo
• Format: Article
• Language: English
• Subjects: Amidines - pharmacology; Amidines - therapeutic use; Animals; Dogs; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; hemodialysis-related hypotension; Heterocyclic Compounds, 2-Ring - pharmacology; Heterocyclic Compounds, 2-Ring - therapeutic use; Hypotension - drug therapy; Hypotension - enzymology; Kidney Diseases - drug therapy; Kidney Diseases - enzymology; Kidney Diseases - physiopathology; Kidney Function Tests; Male; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; ONO-1714; Renal Dialysis - methods; ultrafiltration
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.scz040430

The effect of a selective inducible nitric oxide synthase inhibitor, ONO-1714 ((1S,5S,6R,7R)-7-chloro-3-imino-5-methyl-2-azabicyclo[4.1.0]heptane hydrochloride), on hemodialysis-related hypotension was investigated using a canine model of renal dysfunction. Renal dysfunction was induced in dogs by complete bilateral ligation of renal arteries. On performing hemodialysis with ultrafiltration, the blood pressure of the renal dysfunction dogs gradually decreased and persisted at reduced levels until completion. ONO-1714 ameliorated the hemodialysis-induced hypotension in the renal dysfunction dogs at a dose that did not influence blood pressure in non-hemodialysis dogs with normal renal function. The above findings indicated that ONO-1714 may elicit beneficial effects on hemodialysis-related hypotension.