Effects of thromboxane A2 receptor blockade on oliguric ischemic acute renal failure in conscious rats.
To investigate the potential pathogenetic and therapeutic roles of thromboxane A2 (TXA2) and its receptor blockade, respectively, in the early phase of ischemic acute renal failure (ARF), renal function, TXB2 excretion, and the effects of the specific TXA2 receptor antagonist sulotroban (SU) in a model of unilateral renal artery occlusion in conscious female Sprague-Dawley rats were studied. Occlusion of the left renal artery for 1 h in untreated (i.e., vehicle-treated) rats (N = 8) resulted in oliguric ARF. In SU-treated rats (N = 8), the drug was given as an i.v. bolus of 5 mg/kg body wt, followed by a continuous infusion of 0.5 mg/min.kg body wt from 1 h before and during ischemia and for 6 h after reflow. After 1 h of ischemia, urine volume of left ischemic kidneys from untreated rats had decreased from 13.2 +/- 2.8 to 1.0 +/- 0.3 and 0.5 +/- 0.2 microL/min.100 g at 2 and 6 h of reflow, respectively, and GFR had decreased from 0.32 +/- 0.04 mL/min.100 g body wt to undetectable values. At 6 h of reflow, medullary Na-K-ATPase was slightly (P < 0.05) reduced in left ischemic kidneys, whereas medullary and papillary enzyme activities were compensatorily increased (P < 0.01) in right intact kidneys. The ADP/O ratio of cortical mitochondria was 41% (P < 0.05) and ATP synthesis was 77% (P < 0.01) lower than in right intact kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
Kramer
H J
HJ
Department of Medicine, University of Bonn, Germany.
Mohaupt
M G
MG
Pinoli
F
F
Bäcker
A
A
Meyer-Lehnert
H
H
Schlebusch
H
H
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D007511:Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism; D009846:Oliguria / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000652:urine
D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013929:Thromboxane B2; C040624:sulotroban; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium