Failure of anti-inflammatory steroids to inhibit prostaglandin release from the hydronephrotic rabbit kidney

The release of prostaglandins E₂, F₂, I₂ and thromboxane A₂ from isolated perfused normal and hydronephrotic rabbit kidneys was investigated by extraction and radio-immunoassay. 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 g (e.g., bradykinin, angiotensin II, substance P, noradrenaline and vasopressin) caused release of additional amounts of prostaglandins. PGE₂ and 6-keto PGF₁ were the major prostanoids detected, but substantial amounts of PGF₂ 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, 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.