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To examine the role of serine proteases in the control of aldosterone (Ald) secretion, we studied the effects of nafamostat mesilate (Naf), a serine protease inhibitor, on in vivo Ald secretion and Ald content in the rat adrenal gland. Either Naf (2 mg/kg/h; n=10) or saline (2 ml/h; n=10) was administered intravenously for 30 min to anesthetized Wistar rats whose left adrenal vein was cannulated selectively via the inferior vena cava. Naf caused a significant decrease in Ald secretion rate compared to saline (1.99+/-0.32 vs. 3.42+/-0.56 ng/min, p &lt;0.001), while adrenal blood flow, mean arterial pressure and plasma renin activity in the adrenal venous blood did not differ between the two groups. In a separate trial, adrenal Ald content, adrenal renin content, plasma adrenocorticotropic hormone (ACTH) and plasma potassium did not differ between rats treated with Naf (n=7) and those administered saline (n=7). These data suggested that Naf-inhibitable serine proteases may participate in the control of Ald secretion through mechanism(s) other than hemodynamic changes, adrenal renin, ACTH, and/or plasma potassium.

A Serine Protease Inhibitor, Nafamostat Mesilate, Suppresses Aldosterone Secretions In Vivo