angiotensinogen and Respiratory-Distress-Syndrome

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Female; Humans; Male; Middle Aged; Respiratory Distress Syndrome

Accumulating evidence shows that angiotensin II (ANG II) can be generated locally in the lung tissue and may have autocrine and/or paracrine actions on the cellular level. In addition, ANG II precursor, angiotensinogen, as well as ANG II type 1 receptor (AT(1)), are also expressed in the lung tissue. Recent studies revealed that ANG II promoted acute lung injury induced by acid aspiration or sepsis, and that ANG II receptor blockade had a protective effect against acute lung injury. Therefore, the authors hypothesized that ventilator-induced lung injury might also be exacerbated by local ANG II action, and that ANG II receptor blockade would protect the lung from ventilator-induced lung injury.. Forty Sprague Dawley rats weighing 300-350 g were randomly divided into the following experimental groups (10 rats in each group): (1) control group: rats were unventilated; (2) LVT (low volume ventilation) group: rats were ventilated with 8 mL/kg tidal volume room air for 2 h; (3) HVT (high volume ventilation) group: rats were ventilated with 40 mL/kg tidal volume room air for 2 h; (4) HVT + Losartan group: rats were pretreated with Losartan (30 mg/kg, i.p.) prior to high volume ventilation. The samples of pulmonary tissue and lung lavage fluid were collected after experiments. The expression of angiotensinogen and AT(1) receptor mRNA in lung tissue was measured by reverse transcriptase-polymerase chain reaction. Apoptosis of the lung cells was assayed with terminal deoxynucleodityl transferase-mediated nick-end labeling method. Lung pathological changes were examined with optical microscopy. Total protein, wet/dry ratios (W/D), myeloperoxidase (MPO) activity, and neutrophil counts of the lung tissue or lavage fluid were measured with corresponding methods.. Compared with control or LVT, HVT caused significant ventilator-induced lung injury and increased the expression of angiotensinogen and AT(1) receptor mRNA in the lung. Total protein, the number of apoptotic cells, W/D ratio, MPO activity, and neutrophil counts were significantly higher in the HVT group than in the LVT or control group. Pretreatment with Losartan attenuated ventilator-induced lung injury and prevented the increase in total protein, the number of apoptotic cells, W/D ratio, MPO, and neutrophil counts caused by high volume ventilation.. Our study indicates that HVT causes remarkable lung injury and up-regulates angiotensinogen and AT(1) receptor expression of in the lung, and that Losartan, a selective inhibitor of subtype AT(1) receptors for angiotensin II, can relieve acute lung injury caused by high volume ventilation.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensinogen; Animals; Apoptosis; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Losartan; Lung; Male; Neutrophil Infiltration; Peroxidase; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Respiration, Artificial; Respiratory Distress Syndrome; RNA, Messenger

The time-course of plasma angiotensinogen (Ao), elastase-alpha 1-protease inhibitor complex (EL alpha 1PI), antithrombin III (AT III) and C-reactive protein (CRP) have been investigated of six patients suffering from adult respiratory distress syndrome (ARDS). The total plasma Ao level (active and inactive Ao) varied in individuals but was increased up to five-fold. An increasing amount of inactive Ao is found. From the beginning of their stay in the intensive care unit up to five days half of the patients displayed a positive correlation between the plasma CRP and Ao level. The CRP and Ao values were either not or were negatively correlated with the AT III values. In contrast plasma Ao and AT III levels in all patients were positively correlated during a particular period in the subsequent phase of the disease, where there was no or a negative correlation with CRP. The two acute phase reactants CRP and EL alpha 1PI were only correlated in two patients at the beginning of the disease. The markedly increased plasma level at the beginning of the inflammatory disease indicates that Ao is an acute phase reactant, and this is supported by the parallel changes in plasma CRP and Ao levels during the early days of ARDS. The relationship between the plasma levels of Ao and AT III for more than fourteen days suggests similar regulation of these members of the serpin family after termination of the acute-phase.

Topics: Adult; alpha 1-Antitrypsin; Angiotensinogen; Antithrombin III; Bacterial Infections; C-Reactive Protein; Female; Humans; Male; Pancreatic Elastase; Respiratory Distress Syndrome