Ibuprofen or ozagrel increases NO release and l-nitro arginine induces TXA(2) release from cultured porcine basilar arterial endothelial cells.
The vascular resting tone of the porcine basilar artery appears to be mostly maintained by a balance between spontaneously released nitric oxide (NO) from endothelial cells and thromboxane (TX) A(2) from endothelial and smooth muscle cells. However the precise role of the interaction between the above two substances in the control of vascular tone is unclear. We attempted to clarify the interaction between NO and TXA(2) using cultured porcine basilar arterial endothelial cells. The cultured endothelial cells produced NO spontaneously, while TXB(2) (a stable metabolite of TXA(2)) production remained below the detection limit. Ibuprofen (a COX inhibitor) and ozagrel (a TXA(2) synthetase inhibitor) significantly increased the spontaneous production of NO, which was not affected by 1400W (an iNOS inhibitor). l-Nitro arginine (a NOS inhibitor) significantly induced TXB(2) production. These results suggest that NO may inhibit COX or TXA(2) synthetase, and that therefore inhibition of NOS might disinhibit COX or TXA(2) synthetase, subsequently inducing TXA(2) production. On the other hand, as TXA(2) and other contractility-related prostaglandin(s) may inhibit NOS, therefore the inhibition of COX or TXA(2) synthetase might disinhibit NOS, and then increase the spontaneous production of NO in porcine basilar arterial endothelial cells.
Miyamoto
Atsushi
A
Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan. miyamoto@agri.kagoshima-u.ac.jp
Hashiguchi
Yoriko
Y
Obi
Takeshi
T
Ishiguro
Shigeru
S
Nishio
Akira
A
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology*; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D008689:Methacrylates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology*; D013552:Swine; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007097:Imines; D008689:Methacrylates; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D019335:Nitroarginine; D009569:Nitric Oxide; D013929:Thromboxane B2; D013928:Thromboxane A2; D019001:Nitric Oxide Synthase; D013930:Thromboxane-A Synthase; C034364:ozagrel; D007052:Ibuprofen