Role of thromboxane A2 and prostacyclin in uninephrectomy-induced attenuation of ischemic renal injury.
Contralateral uninephrectomy attenuates unilateral renal ischemic injury. The present work was performed to elucidate whether the beneficial effect of uninephrectomy was mediated through the modification of the actions of thromboxane A2 (TxA2) or prostacyclin. Unilateral ischemic injury was provoked by a 60-minute left renal artery occlusion in right nephrectomized (Nx) and in sham-nephrectomized (Sham-Nx) rats. Inulin clearance (CIn) of left kidney 48 hours after ischemia was significantly higher in the Nx group than in the Sham-Nx group (0.11 +/- 0.07 vs. 0.00 +/- 0.00 ml/min/kidney, P < 0.05). Ischemia-induced tubular necrosis was also less in Nx animals. Proliferating cell nuclear antigen (PCNA) staining, a marker for cell proliferation, was found more markedly in Nx rats than in Sham-Nx animals. Forty-eight hours after ischemia, renal cortical TxB2 content was greater in Sham-Nx rats than in Nx rats (29.5 +/- 4.4 vs. 18.3 +/- 1.7 pg/mg protein, P < 0.05). No significant difference was found in the intrarenal content of 6-keto prostaglandin F1 alpha between two ischemia groups. A thromboxane synthetase inhibitor, OKY-046 (100 mg/kg/day, i.p.), significantly increased CIn 48 hours after ischemia (0.00 +/- 0.00 vs. 0.17 +/- 0.09 ml/min/kidney, P < 0.05) and attenuated ischemic tubular damage in Sham-Nx rats but not in Nx animals. Under OKY-046 treatment, no significant difference was found in postischemic CIn and ischemic tubular damage between the Nx and Sham-Nx groups. OKY-046 also increased PCNA expression in the cortex and outer stripe in Sham-Nx animals. These data suggest that less production of intrarenal TxB2 plays an important role for the uninephrectomy-induced attenuation of ischemic renal damage and for the facilitation of tubular recovery.
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
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Kato
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Hishida
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Nakajima
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D011464:Epoprostenol / Q000502:physiology*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009392:Nephrectomy / Q000379:methods; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013194:Staining and Labeling; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000378:metabolism
D008689:Methacrylates; D018809:Proliferating Cell Nuclear Antigen; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; C034364:ozagrel