Changes in A-type natriuretic peptide and its receptors induced by a neutral endopeptidase inhibitor in a rat model of sepsis.
OBJECTIVE
Elevated plasma A-type natriuretic peptide (ANP) levels in sepsis cause fluid transfer into extravascular spaces. We investigated the changes in ANP concentrations and natriuretic peptide receptor (NPR) expression induced by thiorphan, a neutral endopeptidase (NEP) inhibitor, in a rat model of sepsis.


METHODS
Fifteen male rats were divided into three groups: a control group (n = 5), a lipopolysaccharide (LPS) group (n = 5), and an LPS-thiorphan group (n = 5). We measured ANP concentrations in the plasma and lung, and NPR mRNA expression in the lung 4 h after administering LPS, and compared the values with those in the control group.


RESULTS
Plasma and lung ANP levels in the LPS group were significantly higher than those in the control group (P < 0.05), but were significantly decreased by thiorphan administration (P < 0.05). NPR-A mRNA levels did not differ significantly among the groups. NPR-C mRNA levels in the LPS-thiorphan group were significantly higher than those in the other groups (P < 0.05).


CONCLUSIONS
Elevated ANP levels were decreased by thiorphan administration, which increased NPR-C mRNA levels in the lung. Thus, thiorphan might be effective for reducing elevated ANP levels in sepsis.
Maeshiro
Kanetaka
K
Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
Takamori
Shinzo
S
Mifune
Hiroharu
H
Matsuo
Toshihiro
T
Kimura
Norman Y
NY
Honda
Junichi
J
Shirouzu
Kazuo
K
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000032:analysis / Q000097:blood*; D004195:Disease Models, Animal; D008168:Lung / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000032:analysis*; D018805:Sepsis / Q000097:blood* / Q000503:physiopathology; D015244:Thiorphan / Q000494:pharmacology
D011480:Protease Inhibitors; D009320:Atrial Natriuretic Factor; D015244:Thiorphan; D017461:Receptors, Atrial Natriuretic Factor