| Acute lung injury (ALI) is a life-threatening respiratory failure induced by various reasons, and its characteristic pathological changes are damages and an increasing permeability of alveolar-microvascular membrane. The serious stage of ALI is known as acute respiratory distress syndrome(ARDS), of which typical clinical manifestations include progressive dyspnea, refractory hypoxemia, pulmonary hypertension and non-cardiogenic lung edema. Some studies suggest that systemic inflammation, proinflammatory cytokines, neutrophils sequestration and activation in the pulmonary microvasculature and surfactant dysfunction be closely related with the pathogenesis of ALI. Atrial natriuretic peptide(AMP), a peptide mainly secreted in the right atrium, is an important regulator of the sodium and volume homeostasis. It has strongly vasodilating effects, diuresis, natriuretic effects and improving microcirculation. There are widely distribution of ANP and its receptors in pulmonary tissues. It is important for regulation of pulmonary circulation and ventilation. Using ANP to therapy pulmonary hypertension and heart failure is effective, which suggest that ANP might play an important role in pathogenesis of ALI. AIM: To investigate whether ANP has effects on ALI induced by LPS in rat and its potential mechanism.Methods: 1)After intravenous injection LPS and LPS incorporate with ANP, mean arterial blood pressure (MAP) .nitric oxide (NO) and-5-endothelin (ET) concentration of plasma, lung water as well as pulmonary histopathological changes were observed respectively in ALI rat induced by IPS. 2) Relaxation and contraction effects of pulmonary and aortae artery were measured by the perfusion of blood vessel rings which come from endotoxemia rat in vitro. Results: 1) Administration of IPS elicited a persistence decrease inMAP( 8. 13?. 57kPa at 4h). AMP could maintain MAP at higher levels (13. 35?. 93kPa, at 4 h, P<0. 05)after an transient decline when IPS was injected.2) NO and ET concentration of plasma was evident higher in IPS group than in control group respectively (P<0. 01). Comparing with LPS group, NO and ET concentration of plasma in AMP group had significantly decrease respectively (P<0. 05).3) Wet-dry ratio of lung in ANP group (4. 57?. 35) was lower than in LPS group (5.15 + 0.43) (P<0.05) and the ratio was not evident difference (P>0. 05) comparing with control group (4. 59?. 24) .4) In LPS group, leukocytes infiltration and alveolus detelectasis can be seen and pulmonary mesenchyme was thicker than control group, no akaryocytes and leukocytes in alveolus, which show an interstitial pulmonary edema. In ANP group, the lung histopathological displays markedly improved.5) Sensitiveness of NE-induced contraction of aorta artery In LPS group was attenuated and EC* was greater comparing with control group (P<0. 01), but its strength was reinforced because E? was bigger (P<0.01). In ANP group, the NE-induced contractility was similar to LPS group (P>0.05). Comparing with control group, NE-induced-6-contraction of pulmonary artery exposured to LPS was reinforced especially in SXlCT'mol ?L"'?0~6mol ?L~'of NE(P<0. 01) and its ECso was obviously higher (P<0. 05). There was no significant difference between AMP therapy group and control group in contraction of pulmonary artery (P>0. 05).6) In ANP therapy group, Ach-induced relaxation and its sensitiveness of pulmonary and aorta artery were evidently improved respectively (P<0. 01)and their ECso decreased comparing with LPS group (p<0. 01); SNP-induced relaxation and sensitiveness of pulmonary and aorta artery were evidently improved respectively (P<0.05)and their ECso decreased comparing with LPS group (p<0. 05).Conclusion: ANP can attenuate ALI and regulate arterial blood pressure and suppress the reinforcing of NE-induced contraction of pulmonary artery exposured to LPS and partly or completely reverse the attenuation of Ach and SNP-induced relaxation of pulmonary and aorta artery in endotoxemia rats. The effects of ANP may be via...
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