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

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>TXB₂6KPGF_1αPGE₂PGF_2α 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_1α. After addition of imidazole, the metabolic profile showed 6KPGF_1αPGE₂HHT>PGF_2α. 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.