PURPOSE: 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.
PURPOSE: 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.
Authors: Rochus Witthaut; Christian Busch; Peter Fraunberger; Autar Walli; Dietrich Seidel; Günter Pilz; Ralph Stuttmann; Norbert Speichermann; Ljifane Verner; Karl Werdan Journal: Intensive Care Med Date: 2003-08-12 Impact factor: 17.440
Authors: P Hamet; J Tremblay; S C Pang; R Garcia; G Thibault; J Gutkowska; M Cantin; J Genest Journal: Biochem Biophys Res Commun Date: 1984-09-17 Impact factor: 3.575
Authors: Nils G Morgenthaler; Joachim Struck; Mirjam Christ-Crain; Andreas Bergmann; Beat Müller Journal: Crit Care Date: 2004-12-17 Impact factor: 9.097