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

Abstract

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 <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.