Role of ANG II in eicosanoid production by isolated glomeruli from rats with bilateral ureteral obstruction

Abstract

The production of prostaglandin (PG) E2, 6-keto-PGF1 alpha, and thromboxane B2 (TxB2) under basal conditions and after exposure to angiotensin II (ANG II) or arginine vasopressin (AVP) was examined in vitro in isolated glomeruli. The glomeruli were obtained from control rats and rats with bilateral ureteral obstruction (BUO) of 24-h duration that were pretreated or not with an inhibitor of the angiotensin I converting enzyme (ACE). Basal prostanoid production was greater in isolated glomeruli from BUO rats than in controls. Administration of an ACE inhibitor, enalaprilat, given in vivo returned basal prostanoid production by isolated glomeruli of BUO rats to levels seen in glomeruli of control rats. The prostanoid production in response to addition of ANG II or AVP in vitro was blunted in glomeruli from BUO rats, but the response was restored to "normal" after blockade of ANG II synthesis in vivo in BUO rats. Blockade of ANG II synthesis in vivo did not affect prostanoid synthesis by isolated glomeruli of control rats. The prostanoid generation in response to addition of both ANG II and arachidonic acid in vitro compared with ANG II addition alone was not significantly stimulated in glomeruli from BUO rats. In contrast, it was significantly stimulated in glomeruli of control rats. The results indicate that endogenous ANG II has an important role in the increased synthesis of prostanoids found in isolated glomeruli of rats with BUO and that the in vitro prostanoid production in response to ANG II and AVP can be restored to normal when the synthesis of ANG II is inhibited in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)