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 greater than TXB2 less than 6KPGF1 alpha greater than PGE2 greater than PGE2 alpha 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 PGF1 alpha. After addition of imidazole, the metabolic profile showed PKPGF1 alpha greater than PGE2 greater than HHT greater than PGF 2 alpha. 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 PGE2 greater than TxB2. 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.
D015121:6-Ketoprostaglandin F1 alpha; D001095:Arachidonic Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D006869:Hydronephrosis / Q000378:metabolism*; D006880:Hydroxy Acids / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D011463:Prostaglandins H / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism*
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids; D007093:Imidazoles; D011458:Prostaglandins E; D011460:Prostaglandins F; D011463:Prostaglandins H; D013931:Thromboxanes; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha