Alterations in rabbit renal microvascular prostanoid synthesis in acute renal failure.
Vasodepressor prostanoids have been suggested to regulate renal hemodynamics after nephrotoxic injury and thus protect the kidney against the effects of prolonged ischemia. This study assessed whether changes in two microvascular vasodilator prostanoids would correlate with changes seen in renal hemodynamics in rabbits with nephrotoxic renal injury produced by either uranyl nitrate or mercuric chloride. Rabbits were killed at 3, 24, and 72 h after the nephrotoxin injections and 6-ketoprostaglandin (PG) F1 alpha and PGE2 synthesis was measured in vitro in isolated renal microvessels. At the end of 24 h, synthesis of both prostanoids was significantly increased in all nephrotoxin-treated animals, an observation not noted at the end of 3 h. At 72 h, 6-keto-PGF1 alpha production remained elevated. Pretreatment with mepacrine blocked the increased prostanoid production seen in uranyl nitrate-treated animals. Thus, renal microvascular vasodilator prostanoid biosynthesis is increased 24-72 h after nephrotoxin administration. These data suggest that the biosynthesis of prostacyclin and PGE2 may contribute to the maintenance of renal blood flow in the first few days after acute renal injury and further suggest that a mechanism for this increase may be stimulation of phospholipase A2.
Chaudhari
A
A
Nephrology Section, Long Beach Veterans Administration Medical Center, California.
Kirschenbaum
M A
MA
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology; D008833:Microcirculation; D011466:Prostanoic Acids / Q000096:biosynthesis*; D011817:Rabbits; D014502:Uranyl Nitrate / Q000494:pharmacology
D005227:Fatty Acids; D011466:Prostanoic Acids; D014502:Uranyl Nitrate; D008627:Mercuric Chloride; D015121:6-Ketoprostaglandin F1 alpha