Rhabdomyolysis is an important cause of
acute renal failure (ARF) and renal vasoconstriction is the main mechanism in the pathogenesis of ARF. Lipid peroxidation due to
hydroxyl radical (.
OH) formation and redox cycling of
myoglobin also have a role. We investigated the disturbance in renal vascular reactivity to reveal the mechanisms leading to ARF. Female Wistar rats (n = 7) were injected with
glycerol (10 mL/kg, 50% in saline) intramuscularly to induce
rhabdomyolysis, and then the kidneys were isolated and perfused. We investigated
acetylcholine (ACh)-induced endothelium-dependent and
papaverine (PAP)-induced endothelium-independent vasodilation responses and renal nerve stimulation (RNS)-induced vasoconstrictions. These were also investigated both in rats which received either .
OH scavenger,
dimethylthiourea (
DMTU: 500 mg/kg before
glycerol injection and 125 mg/kg 8 h after
glycerol injection, n = 7), or
myoglobin redox cycling inhibitor,
acetaminophen (
ApAP: 100 mg/kg 2 h before
glycerol injection and 100 mg/kg each 4 h, and 22 h after
glycerol injection, n = 7). ACh-induced responses in
glycerol group were decreased (p < 0.001), but PAP-induced vasodilation did not change. RNS-induced vasoconstriction in all kidneys was greater (p < 0.001) in
glycerol group.
DMTU restored both endothelium-dependent vasodilation and RNS-induced vasoconstriction.
ApAP had no effect on vascular responses. Both
DMTU and
ApAP exerted a partial protective effect in renal histology without restoring serum
creatinine and blood
urea nitrogen (BUN) levels or
creatinine clearance. This study showed that endothelial dysfunction and increased vasoconstriction developed during
rhabdomyolysis. .
OH plays an important role in the development of these vascular responses. These findings suggest that decreased endothelium-dependent vasodilation and augmented renal sympathetic tonus contribute to the development of renal vasoconstriction during
rhabdomyolysis-induced ARF.