Failure of chronic aspirin treatment to inhibit urinary prostaglandin excretion in spontaneously hypertensive rats: comparison with indomethacin and flurbiprofen.
The inability of chronic treatment with aspirin to cause sustained inhibition of urinary prostaglandin (PG) excretion observed previously prompted us to compare the effects of 9-day treatment of spontaneously hypertensive rats with aspirin, 200 mg/kg/day s.c., flurbiprofen, 2.5 mg/kg/b.i.d. s.c. and indomethacin, 2.5 mg/kg/b.i.d. s.c. on the excretion rate of radioimmunoassayable PGE2 and PGF2 alpha. Conversion of 1-[14C]arachidonic acid and the release of PGs from endogenous substrate by the renal papilla were also examined. In vehicle-treated control rats, PGF2 alpha excretion ranged from 32.2 +/- 6.2 (mean +/- S.E.M.) to 41.6 +/- 7.3 ng/6 h, and was 2- to 4-fold higher than that of PGE2. Within 6 h of administration all three drugs reduced excretion of PGF2 alpha and PGE2 to less than 20% and 35% of control rats, respectively. Thereafter, PGF2 alpha and PGE2 excretion in aspirin-treated rats returned to values similar to the vehicle-treated group, whereas inhibition of PG excretion in indomethacin and flurbiprofen groups was sustained. Urine volume was doubled by aspirin throughout the study. In contrast, urine volume in flurbiprofen- and indomethacin-treated rats was unaffected. Paradoxically, metabolism of 1-[14C]arachidonic acid to PGs by renal papilla dissected on day 10, 2 to 4 h after the last drug dose, was reduced markedly by aspirin as was the release of immunoreactive PGs but was unaffected by flurbiprofen or indomethacin. The failure of long-term aspirin treatment to inhibit urinary PG excretion and the disparity between in vivo and ex vivo indices of PG release emphasize the need to verify their intended action by measuring PGs in biological fluids.
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005480:Flurbiprofen / Q000494:pharmacology*; D006973:Hypertension / Q000652:urine*; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D008297:Male; D011422:Propionates / Q000494:pharmacology*; D011453:Prostaglandins / Q000652:urine*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D011422:Propionates; D011453:Prostaglandins; D005480:Flurbiprofen; D001241:Aspirin; D007213:Indomethacin