Atrial natriuretic peptide (ANP) has been shown to play a crucial role in the regulation of hemodynamics, natriuresis, and vasorelaxation. ANP has physiological receptor (NPR-A) and clearance receptor (NPR-C). ANP is increased in septic state. Thiorphan, one of the neutral endopeptidase (NEP) inhibitors, inactivate ANP, but its physiological role remains unclear. The purpose of this study is to characterize the changes in lung ANP receptor expression by thiorphan administration in septic model.
Wistar male rats were anesthetized with ketamine hydrochloride and were divided into three groups as to Group A, control group (n=5); Group B, LPS administration group (n=5); and Group C, lippopolysaccharide (LPS)+thiorphan administration group (n=5). LPS of 1 ug/kg was intraperitonealy administered in Group B. One hour after the LPS administration, thiorphan was infused with 3.5 mg/kg for 30 min in Group C. The blood and lung tissue were taken in each group at 2 and 4 hrs after the LPS administration. The concentration of ANP was measured by radioimmunoassay, and NPR-A and NPR-C mRNA expression were measured by quantitative PCR. Statistical analyses were performed by ANOVA.
In Group B, plasma ANP concentration at 4 hrs significantly increased compared to those of the other groups (p<0.05). Lung ANP concentration at 4 hrs significantly increased comparing to those of the other groups (p<0.05). The NPR-A mRNA expression at 2 hrs in Group B was significantly higher than the those of the other groups (p<0.05). NPR-C mRNA expression at 4 hrs in Group C was significantly higher than those of the other groups (p<0.05).
Four hrs after the LPS administration, plasma and lung ANP increased significantly, and thiorphan increased NPR-C mRNA expression significantly.
Thiorphan facilitates the exhaust serum ANP via lung NPR-C mRNA elevation in the septic state.
K. Maeshiro, None.