Diltiazem Effect And Mechanism Of Hypoxic Pulmonary Hypertension

Pulmonary hypertension (Pulmonary Artery Hypertension, PAH) is a lung disease which is difficult to diagnose, affecting the patient's quality of life seriously,getting a poor prognosis, has become to be the focus in scientific research, clinical research recently. Hypoxia will lead to pulmonary artery reconstruction, blood vessel wall thickening, stenosis, and lead to pulmonary hypertension and pulmonary heart disease,Calponin (also known as calmodulin) is a kind of smooth muscle-specific calcium-binding protein, and its expression reduces obviously in many cell proliferative disease. Thin filament accommodates the vascular blood pressure through the calpoin's phosphorylation effect on regulating the calcium ion activity. Diltiazem, as a calcium antagonist, interfers with the role of pulmonary artery pressure by inhibiting the calcium ion to the peripheral vessels, coronary vascular smooth muscle cells and atrioventricular node cells of flow.Objects:To study the mechanism of hypoxic pulmonary artery hypertension by simulating high altitude hypoxia, study the relationship between calponin expression in pulmonary artery smooth muscle cell, right ventricular hypertrophy and cardiac function and pulmonary artery hypertension, study the diltiazem effect on hypoxic pulmonary artery hypertension.Methods:We established the rat hypoxic pulmonary artery hypertension model by putting the rats in hypobaric chamber, imitating the hypoxic condition at 5000 metres. The rats were divided into control group, hypoxia group and hypoxia plus diltiazem group, each group were divided into four groups by hypoxic time. Mean pulmonary artery hypertension, right ventricular hypertrophy and cardiac function were evaluated and calponion expression were studied by immunohistochemistry and Western Blot.Results:The hypoxic pulmonary hypertension animal model were successfully established, pulmonary artery pressure, ventricle hypertrophy and dp/dt increased following the prolonged hypoxia time while the calponin expression decreased during this process. The hypoxia plus diltiazem group got a slighter change compared with the hypoxia group.Conclusion:Hypoxia could result in the up-regulation of pulmonary artery pressure while the down-regulation of calponin in pulmonary artery smooth muscle cell, and diltiazem could reduce this degree in this process. Epidemiologic investigations had consistently shown that, systolic blood pressure (SBP) was a much better predictor of cardiovascular risk than diastolic blood pressure (DBP), especially in patients over 50-year-old,a period during which the majority of cardiovascular events occurs. In recent years study, the epidemiology research on the relationship between pulse pressure (PP, pulse pressure, the difference between systolic and diastolic blood pressure) and the cardiovascular disease, showed that increased pulse pressure is a useful significant risk factor of arteriosclerosis and cardiovascular disease. Ministry of Health of the People's Republic of China showed that the mortality of cardiovascular disease and cerebrovascular disease constitutes 17.74% and 21.28% of total mortality, this study about the pulse pressure and related factors of healthy adults in Sichuan is based on the Key Program of Science and Technology Basic Special Foundation (No:2006FY300110).Following the cross-sectional and Stratified cluster sampling principle, there are 3714 people aged>20 are randomly selected in Xinjin City and Qionglai City on Sichuan Province for the physical examination between October 2007 and May 2008. Then 1989 individuals (747 males aged of 58.2±13.3 years and 1242 females aged of 54.2±13.4 years) were selected for this study.Pulse pressure, BMI, SBP,DBP and waist-to-hip ratio(WHR) increase following the age especially those who are over 50-year-old, DBP showed a more significant increase than SBP. PP of the people aged over 50 increased linearly, especially for the women during post-menopause.The BMI was divided under WGOC standard, PP,WHR,FGP showed an increasing trend following the BMI. Some of these items increased following the PP group. UA and BUN in men is much higher than women in the same PP group while TC and HDL is much lower.and the relationship between age,BMI,WHR,TG and pulse pressure is linear, physical exercise is in negative correlation to pulse pressure.In summary, this study showed the distribution of pulse pressure and related factors in different gender and age group of 1989 healthy adults in Sichuan. What's more, we studied the relationship of pulse pressure and related factors from different levels, discussed the interventions for the pulse pressure of healthy people and provide basic theory for the prevention of cardiovascular disease.