Involvement of renal sympathetic nerve activation on the progression of ischemic acute kidney injury in the mouse.

Renal ischemia produces renal sympathoexcitation that is responsible for the development of ischemic acute kidney injury. The present study examined changes in the sympathetic nerve function in mice. Ischemic acute kidney injury was induced by occlusion of both renal pedicles. Renal ischemia/reperfusion increased blood urea nitrogen and plasma creatinine and expression of tyrosine hydroxylase, a rate-limiting enzyme for the biosynthesis of noradrenaline, in the kidney. Renal immunoreactivity of tyrosine hydroxylase was observed along with vessel and tubular structure both in the sham-operated and the ischemic acute kidney injury mice. The prominent morphological change was that tyrosine hydroxylase immunoreactivity was observed in the glomeruli of the ischemic acute kidney injury mice, whereas there are almost no tyrosine hydroxylase immunoreactivity signals in the glomeruli of the sham-operated mice. This tyrosine hydroxylase immunoreactivity in the glomeruli is colocalized with synapsin I immunoreactivity in the ischemic acute kidney injury mice. Intraperitoneal pretreatment with DSP-4 (50 mg/kg) attenuated these changes induced by renal ischemia/reperfusion. These results suggest that morphological and functional changes of glomerulus adrenergic nerve terminal are involved in the pathophysiology of ischemia/reperfusion-induced ischemic acute kidney injury.