Prostacyclin and thromboxane A2 moderate postischemic renal failure.
Since prostacyclin (PGI2) is known to regulate renal cortical blood flow and since ischemia stimulates thromboxane (Tx) A2 synthesis, the role of these prostanoids in moderating the response to renal ischemia was studied in the rat. At baseline, plasma TxB2 concentration in untreated animals (n = 13) was 357 pg/ml. The left renal pedicle was clamped for 45 minutes after a right nephrectomy (n = 16), which led after 5 minutes of reperfusion to a rise in TxB2 to 2825 pg/ml (p less than 0.001), but there was no change in 6-keto-PGF1 alpha. After 24 hours creatinine levels rose from 0.4 to 3.0 mg/dl (p less than 0.001), and left renal weight rose from 94% to 117% (p less than 0.001) relative to the weight of the right kidney. In nephrectomized but nonischemic sham control rats (n = 7), creatinine level was 0.9 mg/dl and kidney weight 91% after 24 hours. Pretreatment with OKY 046 (n = 13) (2 mg/kg administered intravenously) blocked ischemia-induced TxB2 synthesis, while 6-keto-PGF1 alpha levels rose from 96 to 302 pg/ml (p less than 0.001). There was no increase in creatinine levels or kidney weight relative to the sham group. Pretreatment with ibuprofen (n = 10) (12 mg/kg) or OKY 046 and ibuprofen (n = 9) inhibited TxB2 and 6-keto-PGF1 alpha synthesis, but creatinine levels and renal weight rose (p less than 0.001). Renal histology in OKY 046-pretreated animals was equal to that in nephrectomized controls, while all other ischemic groups showed tubular necrosis. Results indicate that a high PGI2/TxA2 ratio protects against renal ischemia.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D011464:Epoprostenol / Q000096:biosynthesis* / Q000502:physiology; D007052:Ibuprofen / Q000494:pharmacology; D007511:Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D011292:Premedication; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000502:physiology; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013931:Thromboxanes / Q000096:biosynthesis*
D008689:Methacrylates; D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; C034364:ozagrel; D007052:Ibuprofen