The role of prostaglandin and thromboxane synthesis by the glomeruli in the development of acute renal failure.
Six hours after glycerol (G) injection in normal rats (NR), creatinine clearance (Ccr) decreased while urinary TXB2 (TXA2), 6-keto-PGF1 alpha (PGI2) and PGE2 significantly increased. The administration of OKY-046, a selective TXA-synthase inhibitor in glycerol-treated rats (GTR), significantly prevented the decrease in Ccr (indicating a partial protection against the development of acute renal failure) (ARF) and the increase in urinary TXA2 excretion, while it did not significantly alter urinary prostaglandin (PG) excretion. However, although TXB2 synthesis by the isolated glomeruli (IG) obtained from rats sacrificed 2 and 6 h after G injection was significantly enhanced, PGE2 and 6-keto-PGF1 alpha (6kPGF1 alpha) synthesis was augmented only by the IG obtained from rats killed 6 h after G administration. TXB2 and 6kPGF1 alpha synthesis by the IG obtained from rats killed 24 h after G injection returned to normal levels, while PGE2 synthesis continued to be elevated. Thus the enhanced release of PGE2 and 6kPGF1 alpha observed in intact animals in the early phase of ARF must be of medullary origin, while the augmented release of TXB2 (TXA2) by the IG must be responsible for the afferent arteriolar contraction during the early phase of this syndrome.
Chatziantoniou
C
C
Renal and Vascular Pathology, Broussais Hospital, Paris, France.
Papanikolaou
N
N
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005990:Glycerol; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000096:biosynthesis*
D011453:Prostaglandins; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D015232:Dinoprostone; D005990:Glycerol