Failure of anti-inflammatory steroids to inhibit prostaglandin release from the hydronephrotic rabbit kidney.
The release of prostaglandins E2, F2 alpha, I2 and thromboxane A2 from isolated perfused normal and hydronephrotic rabbit kidneys was investigated by extraction and radioimmunoassay. In both types of kidneys, basal PG efflux increased with time and was not altered by co-perfusion with dexamethasone or hydrocortisone. Several vasoactive substances at 1 to 4 micrograms (e.g., bradykinin, angiotensin II, substance P, noradrenaline and vasopressin) caused release of additional amounts of prostaglandins. PGE2 and 6-keto PGF1 alpha were the major prostanoids detected, but substantial amounts of PGF2 alpha were also found. Thromboxane A2 was not released from normal kidneys. In hydronephrotic kidneys there was greatly augmented release of prostaglandins E2 and I2, some increases in PGF2 alpha, and the appearance of substantial amounts of thromboxane A2 (measured as immunoreactive TXB2) when the kidneys were challenged with angiotensin, bradykinin and vasopressin, and smaller augmentation of the response to noradrenaline and substance P. There was no evidence that these evoked increases in renal PG output could be inhibited by dexamethasone or hydrocortisone. Some explanations for the failure of steroids to alter prostanoid metabolism from arachidonate in rabbit kidney are discussed, and it is proposed that there are clear exceptions to the concept that steroids inhibit prostaglandin generation in intact tissues.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D003864:Depression, Chemical; D006869:Hydronephrosis / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D013929:Thromboxane B2 / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D011453:Prostaglandins; D014667:Vasopressins; D000804:Angiotensin II; D013929:Thromboxane B2; D001920:Bradykinin; D009638:Norepinephrine