Thromboxane A2 has been known as an important endogenous substance which is related to impariment of renal function. In normal kidney. TXA2 and modulate renal blood flow(RBF0 and glomerular filtration rate(GFR). However in various pathologic
condition,
especially in renal ischemia, RBF and GFR are decreased due to increased of TXA2 production by the renal cells and then renal cells are injured subsequently.
KT2-962 is a slective TXA2/PGH2 receptor antagonist with has antagonistic action for the thromotic and vasoconstrictive activities of TXA2 .
the aim of the present study was to assess the effect of KT2-962 on acute renal ischemia induced by the right nephrectomy and the ligation of left renal vellels for 40 min in 20 male rats(250-300g).
Before induction of ischemia, 40 mg/kg of KT2-962 was administered orally three times with interval of 12hours. Same dose of KT2-962 was administered at 12 hour after reperfusion of renal vessels. Blood samples were taken from femoral vein before
operation and two times after operation at the interval of 24 hors. BUN and serum creatinine concentration were measured by automated chemistry analyzer(SBA-300, Gilfod co).
@ES The results obtained were as follows:
@EN 1. In control group(n=10), BUN levels(means±SD) at 24 , 48 hours after right nepherctomy and ligation of left renal vessels for 40 minutes were 142.3±15.1, 172.6±28.2mg/dl. The BUN levels in the group treated with KT2-962(n=10) were
significantly
decreased to 107.0±9.9, 104.7±10.9mg/dl(p<0.05) respectively. These BUN levels were inhibited 24.8% and 39.3% compared with control group.
2. In control group(n=10), serum creatinine levels(mean±SD)at 24, 48 hours after right nephrectomy and ligation of left renal vessels for 40 min were 5.43±0.84, 6.90±1.26mg/dl. The serum creatinine levels in the group levels in the group
treated
with KT2-962 were significantly decreased to 4.55±0.55, 4.47±0.64mg/dl (p<0.05) respectively. these serum creatinine levels were inhibited 16.2% and 35.2% compared with control group.
In conclusion, KT2-962 inhibited the elevation of BUN and serum creatinine levels ion acute renal ischemia and these results suggest that KT2-962 may be used in the prevention and treatment of severe acute renal ischemia.
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