Mechanism of the decreased eicosanoid production in vitro in response to angiotensin II in glomeruli of rats with bilateral ureteral obstruction

Hiroyuki YANAGISAWA, Nobutaka KURIHARA, Saulo KLAHR, Jerry MORRISSEY, Osamu WADA

Research output: Contribution to journalArticlepeer-review

Abstract

Summary: Glomeruli isolated from rats with bilateral ureteral obstruction (BUO) of 24 h duration synthesized significantly greater amounts of prostaglandin (PG)E2, 6‐keto PGF1a, thromboxane (Tx)B2 and leukotriene (LT)B4 than glomeruli isolated from sham‐operated control (SOC) rats. Glomeruli isolated from SOC rats produced increased amounts of these four eicosanoids compared to basal conditions when 100 nmol/L angiotensin II (AII) was added in vitro to the preparations. However, no significant increases in glomerular eicosanoid production were seen under these conditions in glomeruli of rats with BUO. to examine the mechanims underlying imparied eicosanoid production in glomeruli of rats with BUO exposed to AII in vitro, we measured the activities of phosphatidylethanolamine (PE)‐specific phospholipase A2 (PLA2), 5‐lipoxygenase and the cyclo‐oxygenase pathway enzymes including cyclo‐oxygenase, PGE2 isomerase and PGI2 and Tx synthases under basal conditions and after addition of 100 nmol/L AII in vitro in glomeruli isolated from SOC rats and rats with BUO of 24 h duration. the basal activities of all of these enzymes were significantly greater in glomeruli of rats with BUO compared to SOC rats. In glomeruli of SOC rats, the activities of these enzymes were markedly increased when exposed to 100 nmol/L AII in vitro compared to basal conditions. By contrast, no significant changes in the activities of enzymes involved in eicosanoid formation above baseline were seen in glomeruli of rats with BUO exposed to AII in vitro. the production rates of eicosanoids paralleled the activities of these enzymes under basal and AII‐stimulated conditions in glomeruli obtained from SOC rats and rats with BUO. Thus, the lack of increased levels of PGE2, 6‐keto PGF1a, TxB2 and LTB4, when glomeruli of rats with BUO of 24 h duration are exposed to 100 nmol/L AII in vitro, maybe due mainly to either the action of PE‐specific PLA2 or the combined action of PE‐specific PLA2, cyclo‐oxygenase pathway enzymes and 5‐lipoxygenase set at, or near, maximum levels as a consequence of BUO.

Original languageEnglish
Pages (from-to)191-197
Number of pages7
JournalNephrology
Volume1
Issue number3
DOIs
StatePublished - Jun 1995

Keywords

  • angiotensin II
  • eicosanoid
  • obstruction

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