Journal of hypertension
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Journal of hypertension · Jan 2009
Camostat mesilate inhibits prostasin activity and reduces blood pressure and renal injury in salt-sensitive hypertension.
Prostasin, a glycosylphosphatidylinositol-anchored serine protease, regulates epithelial sodium channel (ENaC) activity. Sodium reabsorption through ENaC in distal nephron segments is a rate-limiting step in transepithelial sodium transport. Recently, proteolytic cleavage of ENaC subunits by prostasin has been shown to activate ENaC. ⋯ Oral administration of camostat mesilate to Dahl salt-sensitive rats fed a high-salt diet resulted in a significant decrease in blood pressure with elevation of the urinary Na/K ratio, decrease in serum creatinine, reduction in urinary protein excretion, and improvement of renal injury markers such as collagen 1, collagen 3, transforming growth factor-beta1, and nephrin. These findings suggest that camostat mesilate can decrease ENaC activity in M-1 cells probably through the inhibition of prostasin activity, and that camostat mesilate can have beneficial effects on both hypertension and kidney injury in Dahl salt-sensitive rats. Camostat mesilate might represent a new class of antihypertensive drugs with renoprotective effects in patients with salt-sensitive hypertension.