Reduced renal ClC-5 Cl- channel expression in spontaneously hypertensive rats with microalbuminuria

Mutations in a renal-specific Cl(-) channel, ClC-5, result in low-molecular-weight proteinuria. Herein we studied ClC-5 expression in the kidneys of spontaneously hypertensive rats (SHR) to identify possible causes of their increased urinary excretion of albumin. The amount of ClC-5 protein was significantly reduced in 3-month-old SHR as compared with normotensive Wistar/Kyoto (WKY) rats. The ClC-5 protein level was partially restored by short term administration of perindopril, an inhibitor of angiotensin-converting enzyme. Corresponding to the increase in ClC-5 expression, the albuminuria in SHR improved to the control level. These results implicate the ClC-5 Cl(-) channel reduction in the development of albuminuria in the early stage of essential hypertension.