Thromboxane A2 is the major arachidonic acid metabolite of human cortical hydronephrotic tissue

Aubrey R. Morrison, Fergus Thornton, Alan Blumberg, E. Darracott Vaughan

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Human cortical hydronephrotic microsomes converted [14C] arachidonic acid to [14C] thromboxane B2 as the major metabolic product. Using [14C] PGH2 as substrate, similar enzymatic conversions were noted with HHT>TXB26KPGFPGE2PGF as the major products. Inhibition of thromboxane synthetase with imidazole 5 mM reduced thromboxane B2 production by 60% and the major product then was 6 keto PGF. After addition of imidazole, the metabolic profile showed 6KPGFPGE2HHT>PGF. Control experiments were carried out using normal cortical tissue obtained from kidneys removed surgically for carcinoma of kidney and rejected for transplantation secondary to fracture as a consequence of blunt trauma. These control kidneys, while they demonstrated an ability to generate thromboxane B2 in vitro, had much less activity than hydronephrotic kidneys and with PGH2 as substrate PGE2TxB2. In addition, inhibition with imidazole produced mainly PGE2. Thus, like the rabbit and rat, there is enhanced thromboxane and prostacyclin synthesis in human ureteral obstruction and are, therefore, potential vasoactive compounds which may in part be responsible for the hemodynamic alterations occurring in human obstructive uropathy.

Original languageEnglish
Pages (from-to)471-481
Number of pages11
JournalProstaglandins
Volume21
Issue number3
DOIs
StatePublished - Mar 1981

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