title: The protective effect of thromboxane synthetase inhibition on renal function in systemic sepsis.
abstract: To study the role of thromboxane in systemic sepsis and renal failure, peritonitis was induced surgically in 22 sheep, leading to local and systemic sepsis. A selective thromboxane synthetase inhibitor, U63,557A (Upjohn Co, Kalamazoo, MI) was given before surgery in five animals and 30 minutes after surgery in five animals. A typical picture of volume-loaded, normotensive, vasodilated septic shock developed in all animals. Twenty four hours after induction of sepsis, the control group showed a marked reduction in glomerular filtration rate (GFR), urine volume, and urinary sodium excretion. Pretreated animals showed no change in GFR and a smaller reduction in urine volume and sodium excretion. The posttreatment group showed no change in any parameters of renal function. Plasma renin activity, urinary TXB2 excretion, and urinary 6-keto PGF1 alpha excretion increased after 24 hours only in the control group. Urinary TXB2 excretion was reduced by 80% in animals given U63,557A before surgery. The results indicate a significant protective effect of U63,557A on renal function during septic shock, probably related to reduced thromboxane synthesis, with no apparent deleterious systemic effects. The results support a role for thromboxane in the pathogenesis of acute renal failure in systemic sepsis.
authors.affiliation: Department of Medicine, University of Western Ontario, London, Canada.
authors.forename: A D
authors.initials: AD
authors.lastname: Cumming
authors.forename: J W
authors.initials: JW
authors.lastname: McDonald
authors.forename: R M
authors.initials: RM
authors.lastname: Lindsay
authors.forename: K
authors.initials: K
authors.lastname: Solez
authors.forename: A L
authors.initials: AL
authors.lastname: Linton
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D009318:Natriuresis / Q000187:drug effects; D010538:Peritonitis / Q000503:physiopathology; D012756:Sheep; D012772:Shock, Septic / Q000503:physiopathology* / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013931:Thromboxanes / Q000502:physiology
chemical_list: D001572:Benzofurans; D013931:Thromboxanes; D013930:Thromboxane-A Synthase; C039936:furegrelate