Effects of five non-steroidal anti-inflammatory drugs on the renal and systemic responses to arachidonate in conscious dogs.

Abstract

1. The effects of five different non-steroidal anti-inflammatory drugs (NSAID) on the renal blood flow responses to arachidonate were compared. 2. Arachidonate (5-200 micrograms/kg) injected into the renal arteries of conscious dogs caused dose-related renal vasodilatation with no systemic effects. 3. Aspirin (35 mg/kg), phenylbutazone (12 mg/kg) and ibuprofen (25 mg/kg) all markedly reduced arachidonate-induced renal vasodilatation. 4. In contrast, neither indomethacin (3 mg/kg) or its related drug sulindac sulphide (6 mg/kg) significantly reduced arachidonate-induced renal vasodilatation. 5. All NSAID abolished the hypotensive response to intravenous injection of arachidonate (10 mg). 6. Thus, indomethacin and sulindac did not block the effects of renal artery injections of arachidonate but did abolish the systemic effects. Aspirin, phenylbutazone and ibuprofen greatly reduced responses to both renal artery and intravenous arachidonate. 7. Indomethacin and aspirin both reduced the production of prostaglandin E2 and 6-keto-PGF1 alpha by dog renal cortical microsomes in vitro. 8. Thus, indomethacin and sulindac had different effects to other NSAID on arachidonate-induced renal vasodilatation. The results are compatible with the hypothesis that some sites of prostaglandin production in the kidneys of conscious dogs may be relatively resistant to inhibition by indomethacin and sulindac.