Y-26763, a
benzopyran derivative, is a newly developed
ATp-sensitive K channel opener and has been reported to protect against ischemic
acute renal failure (ARF). We examined the effects of
Y-26763 on glycerol-induced myoglobinuric ARF in the rats. ARf was induced in 28 adult male Sprague-Dawley rats by hind-limb
intramuscular injection of 50%
glycerol (5 ml/kg) after 18 hrs of water deprivation.
Y-26763, 7 micrograms/kg (GY group, n = 10) of vehicle (G group, n = 12) was given intravenously 15 min before
glycerol injection.
Glibenclamide (20 mg/kg), a K channel blocker was given prior to
Y-26763 injection to see of the effects was due to the K-channel opener (GYG group, n = 6). Animals were sacrificed 24 or 96 hrs after
glycerol injection.
Y-26763 partially, but significantly, restored renal dysfunction 24 hrs after ARF. Pcr (mg/dl) and Ccr (ml/min), respectively were as follows: G group, 5.7 +/- 0.4, 0.015 +/- 0.006; GY group, 4.1 +/- 0.4, 0.061 +/- 0.027 (p < 0.05). These favorable effects were antagonized by
glibenclamide (Pcr in GYG group, 5.4 +/- 0.3 mg/dl, p < 0.05). Renal
calcium content was not statistically significant (3.5 +/- 1.2 vs. 3.4 +/- 1.2 micrograms/mg dry weight). Histological examinations revealed that extensive tubular
necrosis and cast formation seen in the G group were reduced in the GY group. At the recovery phase, 96 hrs after
glycerol injection,
Y-26763 accelerated the recovery from ARF as shown in Pcr (mg/dl) and Ccr (ml/min): 4.3 +/- 0.2, 0.05 +/- 0.01 in the G group, 2.8 +/- 0.2, 0.13 +/- 0.02) in the GY group (p < 0.01). In conclusion,
Y-26763 partially protected against
glycerol-induced ARF.