thromboxane-a2 and imidazole-2-hydroxybenzoate

The behavior of imidazole 2-hydroxybenzoate (ITF 182), acetylsalicylic acid (ASA) and indometacin (INN; in some pharmacopoeias called indomethacin) in inhibiting thromboxane A2 (TXA2) and prostaglandin (PGs) production in the blood of the rat intravenously injected with arachidonic acid was studied. ITF 182 caused a selective inhibition of TXA2 production with a time-dependent reversible action. An irreversible inhibition of PGs production was shown by ASA whereas a reversible inhibition could be observed with indometacin. The PGs involved in the physiological processes, may be spared after ITF 182 administration contrary to what occurs after ASA or indometacin administration.

Topics: Animals; Anti-Inflammatory Agents; Arachidonic Acid; Arachidonic Acids; Aspirin; Cyclooxygenase Inhibitors; Imidazoles; Indomethacin; Injections, Intravenous; Male; Prostaglandins; Rats; Rats, Inbred Strains; Salicylates; Thromboxane A2; Thromboxane-A Synthase; Thromboxanes

Superfused rings of rabbit basilar arteries are more sensitive than those of saphenous arteries to the contractions induced by a prostaglandin endoperoxide analogue (U-46 619) and by a thromboxane A2 (TXA2) generating system. 5-Hydroxytryptamine aggravates the latter. Prostaglandin I2 (PGI2) on the other hand, relaxes only the basilar rings without affecting the saphenous. Imidazole 2-hydroxybenzoate (ITF 182), at doses that do not interfere with platelet cyclooxygenase, reduces the contractions induced by the TXA2 generating system on both arteries because it reduces the platelet TXA2 synthetase enzyme. TXA2 is involved in the aetiology of strokes and cerebral vasospasms while PGI2 plays a physiological role in the maintenance of cerebral arterial tone. The high sensitivity of cerebral arteries to contractures caused by TXA2 together with the ability of ITF 182 to reduce them by inhibiting TXA2 production and to spare physiological PG production suggest a beneficial effect of the drug in cerebral vasospasms.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Anti-Inflammatory Agents; Arteries; Basilar Artery; Dinoprostone; Imidazoles; In Vitro Techniques; Leg; Male; Muscle Contraction; Muscle, Smooth, Vascular; Prostaglandin Endoperoxides, Synthetic; Prostaglandins E; Rabbits; Salicylates; Thromboxane A2; Thromboxanes

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Central Nervous System; Death, Sudden; Imidazoles; In Vitro Techniques; Kinetics; Male; Mice; Platelet Aggregation; Rabbits; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Stomach Ulcer; Thromboxane A2; Thromboxanes