title: 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.
authors.affiliation: Department of Cardiovascular Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, Japan.
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Tetsuo
authors.forename: Shinji
authors.initials: S
authors.lastname: Seto
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Shoichi
authors.initials: S
authors.lastname: Nagao
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Ozeki
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Masazumi
authors.initials: M
authors.lastname: Akahoshi
authors.forename: Katsusuke
authors.initials: K
authors.lastname: Yano
mesh_terms: D000311:Adrenal Glands / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism*; D000450:Aldosterone / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001550:Benzamidines; D001794:Blood Pressure / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012083:Renin / Q000032:analysis; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001550:Benzamidines; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D000450:Aldosterone; D012083:Renin; C032855:nafamostat