Production of thromboxane A2 by the kidney in glycerol-induced acute renal failure in the rabbit.
The hemodynamic alterations occuring in glycerol induced renal failure are controversial. To date no single humoral substance can fully explain the change in renal resistance observed in this hemodynamic model of acute renal failure. To assess the capacity of the rabbit kidney to produce thromboxane A2, a potent vasoconstrictor, the following experiments were carried out. Rabbits received 14 ml/kg of 50% glycerol subcutaneously 24 hrs before the study. After 24 hrs., the kidneys were removed and perfused ex vivo in superfusion bioassay cascade. Kidneys from rabbits which developed renal failure, as assessed by elevated serum creatinines, released a substance which produced contraction of rabbit aorta (RCS) in response to bradykinin (BK) and angiotensin II. Microsomes prepared from these kidneys when incubated with [14C]-arachidonic acid produced a peak of radioactivity which comigrated with thromboxane B2 on the thin layer chromatography and was inhibited by the thromboxane synthetase inhibitor imidazole. Furthermore, an inverse linear relation was found between the BK dose required to release RCS from perfused kidney and the serum creatinine levels. A direct linear relation was found between the percent of TxB2 produced by renal microsome preparations and the serum creatinine. These studies demonstrate an increased renal capacity of the glycerol-model of acute renal failure to produce TxA2. The production of TxA2 a potent vasoconstrictor should therefore be further evaluated as a potential endogenous mediator of the hemodynamic changes occurring in acute renal failure.
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D003404:Creatinine / Q000097:blood; D005990:Glycerol / Q000494:pharmacology*; D006439:Hemodynamics; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D013931:Thromboxanes; D013928:Thromboxane A2; D003404:Creatinine; D005990:Glycerol