| Background Obstructive sleep apnea syndrome (OSAS) is a chronic sleep-related respiratory disease and is common in clinical practice. The prevalence of OSAS in adults is 2%-4%. OSAS is characterized by repetitive prolonged cessation of airflow at the upper airways, associated with recurrent episodic hypoxia in sleep. In recent years, epidemiological and clinical studies confirmed that, OSAS is an independent risk factor of coronary artery disease (CAD), however; the underlying mechanism remains unclear. Patients with both CAD and OSAS are difficult to treat. So it is important to understand the pathogenesis. Studies showed that, decreased fibrinolytic function is positively correlated with the risk of developing CAD, and patients with OSAS may exhibit decreased tissue plasminogen activator (t-PA) activity and increased plasminogen activator inhibitor-1 (PAI-1) activity. It has been suggested that, low fibrinolytic activity might represent one of the factors that cause the high incidence of CAD in patients with OSAS.Objective The purpose of this study was to observe the dynamic changes of the fibrinolytic system, renin-angiotensin system (RAS) and catecholamines during the development of chronic intermittent hypoxia (CIH) in rats, and to evaluate their roles in the cause of high prevalence of CAD in patients with OSAS.Methods 72 male Wistar rats were divided randomly and equally into three groups as follows; intermittent hypoxia group (IH), Sham control group (SC) and unhandled control group (UC). Using 30-seconds infusion of nitrogen and followed by 30-seconds infusion of compressed air into exposure chambers(4%-6% nadir ambient oxygen with return to 21%), IH rats were subjected into intermittent hypoxia every 60 seconds for 8h/day during the diurnal sleep period; SC rats were similarly handled, but received compressed air instead of nitrogen. And UC rats remained unhandled. The rats were killed on day 7,2land 42 after experiment respectively, and 8 rats were killed each time in each group. The following indexes were observed: (1) The level of t-PA and PAI-lactivity in plasma (spectrophotometric assay); (2) The expression of t-PA and PAI-1 mRNA in tissues (RT-PCR); (3) The level of renin and AT II activity in plasma (radioimmunoassay); (4) The level of norepinephrine and epinephrine in plasma.Results (1) The plasma t-PA activity in IH rats were reduced mildly and gradually over time, the t-PA activity in IH rats were 0.55 + 0.19IU/ml, 0.52 + 0.20 IU/ml and 0.49 + 0.22 IU/ml on day7,21and 42 respectively, but the differences among IH, UC and SC were not significant (P>0.05); The PAI-1 activity were 0.70 + 0.06 AU/ml, 0.71+0.05 AU/ml and 0.75+0.08 AU/ml on day 7,2land 42 respectively, showing no difference compared with that in two control groups (P>0.05). (2) In IH rats, the expression of t-PA mRNA in the heart, kidney, liver and aorta tissues showed no difference compared with that in two control groups on day7, 21 and 42 (P>0.05); In the heart and liver, the level of PAI-1 mRNA showed time-dependent increase, but the difference was not significant compared with that in two control groups. The level of PAI-1 mRNA in kidney and aorta, showed no differences compared with that in two control groups. (3) The plasma renin and ATII in IH rats, increased gradually over time, the level of renin began to increase significantly on day 7(0.31+0.11 ng/ml/h), 21(0.43 + 0.21 ng/ml/h) and 42(0.54+0.24 ng/ml/h) respectively compared with that in two control groups (P<0.05); The level of AT II (345.54+76.01 pg/ml) showed no difference compared with that in other two groups on day 7 , but on day 21(406.11+63.68 pg/ml) and 42 (422.81+67.12 pg/ml), the level of ATIIincreased significantly compared with that in other two groups(P<0.05). (4) The plasma level of epinephrine in IH rats, showed time-dependent increase, but no statistical differences were found compared with that in two control groups; The level of norepinephrine showed time-dependent increase, however, the level had no difference on day 7(502.00 + 117.68 ng/1),...
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