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(Hypertension. 2005;46:683.)
© 2005 American Heart Association, Inc.

Original Articles

Urinary Prostasin

A Candidate Marker of Epithelial Sodium Channel Activation in Humans

Oliviero Olivieri; Annalisa Castagna; Patrizia Guarini; Laura Chiecchi; Gherardo Sabaini; Francesca Pizzolo; Roberto Corrocher; Pier Giorgio Righetti

From the Department of Clinical and Experimental Medicine, Unit of Internal Medicine (O.O., A.C., P.G., L.C., F.P., R.C.), and Department of Science and Technology (A.C., G.S., P.G.R.), University of Verona, Italy.

Correspondence to Oliviero Olivieri, Dip.to Medicina Clinica e Sperimentale, Cattedra di Medicina Interna, Università di Verona, Policlinico Borgo Roma, 37134 Verona, Italy. E-mail oliviero.olivieri{at}univr.it

Prostasin is a serine peptidase hypothesized to regulate epithelial sodium channel (ENaC) activity in animals or on in vitro cultured cells. We investigated whether urinary prostasin may be a candidate marker of ENaC activation in humans. We studied 10 healthy volunteers and 8 hypertensive patients with raised aldosterone-to-renin ratio before and after spironolactone or saline/Florinef suppression test, respectively. Four healthy subjects were also studied before and after saline. Urinary prostasin was evaluated by SDS-PAGE, 2D maps, and Western blotting. Every sample of normotensive individuals was compared with the corresponding sample of urine collected after spironolactone or saline; every sample of hypertensive patients was compared with the corresponding sample of urine collected after saline or Florinef. Prostasin was detectable in all subjects regardless of gender, dietary sodium intake, and spironolactone treatment. Spironolactone (100 mg) increased urinary Na⁺/K⁺ ratio and decreased urinary prostasin in normotensives in whom the renin/aldosterone axis was activated by a low Na⁺ intake, but it was ineffective in individuals with high Na⁺ intake. Saline infusion also reduced prostasin in normotensive subjects. In contrast, prostasin paradoxically increased in urine of patients affected by primary aldosteronism after volume expansion. By 2D immunoblotting, several protein isoforms were observed, some of them being overexpressed after inhibition tests in patients with primary aldosteronism. In addition to a "basal" aliquot of prostasin, constitutively released in human urine regardless of sodium balance and aldosterone activation, there exists a second "aldosterone-responsive" aliquot modulated by Na⁺ intake and potentially suitable as candidate marker of ENaC activation.

Key Words: aldosterone • renin • sodium • ions • mineralocorticoids • hypertension • sodium channels

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