Interaction between non-steroidal antiinflammatory agents and sodium salicylate in the relaxant response of dog renal arteries to angiotensin II.

Angiotensin (ANG) II produced a slight, transient contraction followed by a moderate relaxation in dog renal artery strips precontracted with prostaglandin (PG) F2 alpha. Treatment with acetylsalicylic acid indomethacin, ibuprofen and sodium meclofenamate reduced the relaxant response to ANG II or reversed the relaxation to a contraction, but did not significantly alter the relaxant response to PGI2. The inhibitory potencies were in the order of meclofenamate greater than indomethacin greater than ibuprofen greater than acetylsalicylic acid. Sodium salicylate and gentisic acid, metabolites of acetylsalicylic acid, in concentrations up to 5 X 10(-4)M did not influence the ANG II-induced relaxation. Treatment with salicylate (5 X 10(-4)M) prevented the inhibitory effect of acetylsalicylic acid, indomethacin or meclofenamate, whereas combined treatment with salicylate and ibuprofen elicited an inhibition of ANG II-induced relaxations to a similar extent to that seen in preparations treated with ibuprofen alone. It appears that acetylsalicylic acid, indomethacin and meclofenamate share the same mechanism for inhibiting the cyclooxygenase activity, but the mechanism of inhibitory action of ibuprofen differs.