Effect of naftopidil on brain noradrenaline-induced decrease in arginine-vasopressin secretion in rats.
Naftopidil, an α1-adrenoceptor antagonist, has been shown to inhibit nocturnal polyuria in patients with lower urinary tract symptom. However, it remains unclear how naftopidil decreases nocturnal urine production. Here, we investigated the effects of naftopidil on arginine-vasopressin (AVP) plasma level and urine production and osmolality in rats centrally administered with noradrenaline (NA). NA (3 or 30 μg/kg) was administered into the left ventricle (i.c.v.) of male Wistar rats 3 h after naftopidil pretreatment (10 or 30 mg/kg, i.p.). Blood samples were collected from the inferior vena cava 1 h after NA administration or 4 h after peritoneal administration of naftopidil; plasma levels of AVP were assessed by ELISA. Voiding behaviors of naftopidil (30 mg/kg, i.p.)-administered male Wistar rats were observed during separate light- and dark cycles. Administration of NA decreased plasma AVP levels and elevated urine volume, which were suppressed by systemic pretreatment with naftopidil (30 mg/kg, i.p.). Urine osmolality decreased 1 h after NA administration. However, naftopidil by itself had no effect on plasma AVP levels or urodynamic parameters during light- and dark cycles. Our findings suggest that systemic administration of naftopidil could prevent central noradrenergic nervous system-mediated decline in AVP secretion and increase in urine production in rats.
Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan; Department of Pediatrics, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan.
Masaki
M
Yamamoto
Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan.
Takahiro
T
Shimizu
Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan.
Shogo
S
Shimizu
Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan. Electronic address: higasi@kochi-u.ac.jp.
Youichirou
Y
Higashi
Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan.
Kumiko
K
Nakamura
Department of Pediatrics, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan.
Mikiya
M
Fujieda
Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan.
Motoaki
M
Saito
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D017208:Rats, Wistar; D014554:Urination / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D009281:Naphthalenes; D010879:Piperazines; D001127:Arginine Vasopressin; C064357:naftopidil; D009638:Norepinephrine
Arginine-vasopressin; Brain; Naftopidil; Nocturnal polyuria; Noradrenaline