Modulation of Nitric Oxide-dependent Vascular and Platelet Function In-vitro by the Novel Phosphodiesterase Type-V Inhibitor, ONO-1505

• Published in: Journal of pharmacy and pharmacology 1999-12, Vol.51 (12), p.1429-1433
• Main Authors: LAIGHT, DAVID W., ANGGÄRD, ERIK E., CARRIER, MARTIN J.
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; Biological and medical sciences; Cardiovascular system; Cyclic Nucleotide Phosphodiesterases, Type 5; Enzyme Inhibitors - pharmacology; Imidazoles - pharmacology; In Vitro Techniques; Male; Medical sciences; Mesylates - pharmacology; Miscellaneous; Nitric Oxide - physiology; Nitric Oxide Donors - pharmacology; Nitroprusside - pharmacology; Pharmacology. Drug treatments; Phosphoric Diester Hydrolases - metabolism; Platelet Aggregation - drug effects; Rats; Rats, Wistar; Vasodilation - drug effects
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/0022357991777074

We have characterized the in‐vitro modulation of both nitric oxide (NO)‐dependent 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‐methoxyquinazoline methanesulphonate). ONO‐1505 elicited vasorelaxation in the rat isolated aorta. If the concentration of ONO‐1505 was ≤10 μM 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 isolated aorta for 10 min with ONO‐1505 in the presence of L‐NAME potentiated vasorelaxation to the NO‐donor, sodium nitroprusside. Similarly, ONO‐1505, although having no effect on adenosine diphosphate (ADP)‐induced rat platelet aggregation in‐vitro, augmented established anti‐aggregatory effects of sodium nitroprusside. The data therefore show that the novel phosphodiesterase V inhibitor ONO‐1505 augments endogenous and exogenous nitrovasodilator activity in‐vitro; they also imply modulation of the NO pathway in the haemodynamic actions of this compound, previously reported in‐vivo.