Downstream effects of splanchnic ischemia-reperfusion injury on renal function and eicosanoid release.
This study examines the hypothesis that intestinal ischemia-reperfusion (I/R) injury contributes to renal dysfunction by altered renal eicosanoid release. Anesthetized Sprague-Dawley rats underwent 60 min of sham or superior mesenteric artery (SMA) occlusion with 60 min of reperfusion. The I/R groups received either allopurinol, pentoxifylline, 1-benzylimidazole, or carrier before SMA occlusion. In vivo renal artery blood flow was measured by Transonic flow probes, the kidneys were then perfused in vitro for 30 min, and the effluent was analyzed for eicosanoid release and renal function. Intestinal I/R caused a twofold increase in the ratio of renal release of thromboxane B2 to prostaglandin E2 and to 6-ketoprostaglandin F1alpha compared with the sham level, with a corresponding 25% decrease in renal sodium and inulin clearance and renal blood flow. Pentoxifylline or allopurinol pretreatment restored renal eicosanoid release and renal sodium and inulin clearance to the sham level but did not alter renal blood flow. Pretreatment with 1-benzylimidazole restored renal function, eicosanoid release, and renal blood flow to sham levels. These data suggest that severe intestinal I/R contributes to the downregulation of renal function. The decrease in renal function is due in part to toxic oxygen metabolites, which occur in the milieu of altered renal eicosanoid release, reflecting a decrease in vasodilator and an increase in vasoconstrictor eicosanoids.
Rothenbach
P
P
Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Turnage
R H
RH
Iglesias
J
J
Riva
A
A
Bartula
L
L
Myers
S I
SI
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015777:Eicosanoids / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007444:Inulin / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D012964:Sodium / Q000378:metabolism; D013152:Splanchnic Circulation
D015777:Eicosanoids; D007093:Imidazoles; C017062:1-benzylimidazole; D000493:Allopurinol; D007444:Inulin; D012964:Sodium; D010431:Pentoxifylline