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The aim of the study was to evaluate the exhaled nitric oxide (F(ENO)) in clinically stable chronic obstructive pulmonary disease (COPD), its relationship to the severity of the disease, pulmonary function, smoking status, reversibility of airflow limitation, and ICS therapy. The study was conducted in 47 patients with COPD and 40 healthy controls. Flow/volume spirometry and F(ENO) measurement were performed before and after 2 months of ICS therapy. F(ENO) were significantly elevated in current smokers and ex-smoking COPD patients. In both groups of COPD patients inhaled corticosteroids (ICS) therapy caused a significant decrease in F(ENO) without significant changes in FEV1. A positive correlation between initial F(ENO) and postbronchodilator FEV1 (% predicted) was observed in the group of ex-smoking COPD patients, but not in the currently smoking COPD group. In both groups of COPD patients, the initial level of F(ENO) correlated with the reversibility of airway obstruction, the increase in postbronchodilator FEV1 and the decrease in F(ENO) following ICS treatment. F(ENO) increases in patients with stable COPD. ICS therapy decreased elevated F(ENO) levels in these patients without statistically significant changes in lung function. The selection of COPD patients with increased F(ENO) level and partial reversibility of airway obstruction should be helpful in terms of proposed ICS treatment.

The aim of the study was to evaluate the effect of losartan on rat platelet adhesion to fibrillar collagen. Washed platelets were counted before and after 15 minutes incubation with collagen (50 microg/ml) and the percentage of adhering platelets was calculated as the index of their adhesion. When the platelets were incubated with collagen 40.8 +/- 0.3% of the platelets adhered. Losartan produced a dose dependent decrease in a number of adhering platelets both when the drug was administered to the animals ex vivo at doses of 3, 10 and 30 mg/kg (p < 0.01-0.001) or was added to the preparation of washed platelets in vitro in concentrations of 10(-8)-10(-5) M (p < 0.01-0.001). In the next step of the study we assessed the influence of L-NAME (10 mg/kg ex vivo, 30 microM in vitro) and indomethacin (2.5 mg/kg ex vivo, 30 microM in vitro) on the antiadhesive effect of losartan (10 mg/kg ex vivo, 10(-6) M in vitro). Blockade of nitric oxide synthase with L-NAME partially reversed the antiadhesive effect of losartan both ex vivo and in vitro. Indomethacin diminished the inhibitory effect of losartan on platelet adhesion when administered ex vivo, but it failed to modify this parameter when added to the suspension of platelets in vitro. In conclusion, losartan reduces platelet adhesion to fibrillar collagen in a dose-dependent manner. The observed action of losartan seems to be mediated mainly by endothelium- and platelet-derived nitric oxide.

Clinical and experimental data have recently accumulated for antithrombotic action of angiotensin-converting enzyme inhibitors (ACE-1s). We have shown previously that captopril (which contains a thiol group in the moiety) exerts more pronounced antithrombotic activity than does an equipotent dose of enalapril (the drug devoid of the thiol group). To clarify the relative importance of the presence of the thiol group in the molecule versus angiotensin-converting enzyme (ACE) inhibitory properties in the antithrombotic action of captopril, rats were treated with captopril (5 mg/kg twice daily; CAP), epicaptopril (stereoisomer of captopril devoid of ACE-inhibitory properties; 5 mg/kg twice daily; EPI), N-acetylcysteine (3.75 mg/kg twice daily; ACC), enalapril (3 mg/kg once daily; ENA), or distilled water (VEH) for 10 days, per os. After ligation of the vena cava, the incidence of the venous thrombosis and/or the thrombus weight decreased significantly in all but the ENA-treated groups when compared with control rats. The effect of CAP, EPI, and ACC was accompanied by a marked reduction of euglobulin clot lysis time and, with the exception of ACC, by an increase in prothrombin time in the blood collected from the site of the thrombus formation. Antithrombotic activity of EPI was completely abolished by nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or indomethacin, with the parallel reversal of fibrinolytic and coagulation parameters toward normal. Activated partial thromboplastin time, mean blood pressure, and bleeding time were not altered by either of the administered drugs. Thus, we demonstrated that thiol compounds exert antithrombotic activity by increasing fibrinolysis and/or suppression of the extrinsic pathway of the coagulation cascade in a nitric oxide/prostacyclin-dependent manner.

Drugs blocking the renin - angiotensin system, angiotensin converting enzyme inhibitors and AT1 receptor antagonists, among many pharmacological effects may exert an antithrombotic action. The mechanisms, which mediate their antithrombotic activity are associated with enhanced nitric oxide and prostacyclin release or with attenuation of angiotensin II action (Fig. 1, 2). Nevertheless, endothelium plays an important role in this process linking the renin-angiotensin and fibrinolysis / coagulation systems.