Vasodilator prostaglandins (PG) prevent renal damage after ischemia.
Thromboxane (Tx) synthase but not cyclo-oxygenase inhibitors prevent acute tubular necrosis (ATN) after renal ischemia, a phenomenon believed to be due to stimulation of the endogenous production of vasodilating prostaglandins (PG). This study directly tests that vasodilating PG protect against the consequences of renal ischemia. Anesthetized, 500-g rats had right nephrectomy and 45 minutes of left renal pedicle clamping or sham clamping. The rats were treated with intravenous (I.V.) saline 1.9 mL/h starting 40 minutes after clamping or sham clamping. All rats except the sham group (N = 8) were pretreated 1 hour before ischemia with ibuprofen (12 mg/kg) to prevent prostanoid synthesis. Beginning 5 minutes before clamp release, the rats were treated intravenously for 2 hours with: saline vehicle (N = 9), PGE1 400 ng/kg/min (N = 6), nitroprusside 4 micrograms/kg/min (N = 8), or dopamine 3 micrograms/kg/min (N = 11). After 24 hours, sham rat creatinine level was 0.5 mg/dL and weight of the left kidney was 86.5% of the previously removed right kidney. Compared with sham rats, ischemia and saline treatment resulted in a rise in creatinine level to 2.7 mg/dL (p less than 0.05) and a rise in kidney weight to 101.9% (p less than 0.05); PGE1 led to a creatinine level of 1.1 mg/dL, a value lower than that of the rats treated with saline (p less than 0.05), and a kidney weight of 92.0%, a value similar to that of sham rats; nitroprusside and dopamine led to a rise in creatinine levels to 3.2 mg/dL (p less than 0.05) and 2.3 mg/dL (p less than 0.05), respectively, as well as a rise in kidney weight to 108.0% (p less than 0.05) and 105.4% (p less than 0.05), respectively. Histologic examination showed ATN in rats treated with saline, nitroprusside, and dopamine, but not in rats treated with PGE1. These results indicate that PGE1 protects the cyclo-oxygenase-treated kidney against ischemia-induced ATN.
D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D004298:Dopamine / Q000627:therapeutic use; D007052:Ibuprofen / Q000627:therapeutic use; D007511:Ischemia; D007668:Kidney / Q000098:blood supply*; D007683:Kidney Tubular Necrosis, Acute / Q000517:prevention & control*; D008297:Male; D009599:Nitroprusside / Q000627:therapeutic use; D011292:Premedication; D011453:Prostaglandins / Q000502:physiology; D011458:Prostaglandins E / Q000627:therapeutic use*; D051381:Rats; D013930:Thromboxane-A Synthase / Q000502:physiology
D011453:Prostaglandins; D011458:Prostaglandins E; D009599:Nitroprusside; D013930:Thromboxane-A Synthase; D004298:Dopamine; D007052:Ibuprofen