| Background and objectiveHypertension was a frequently-occurring and common disease and did harm to human health seriously. It was the leading cause of death currently. The pathogenesis of hypertension was extremely complex. Except for genetic factors, it is generally believed that environmental factors may be one of the reasons at present. Epidemiological data showed that stress stimulator was the important reason of hypertension. Noise can cause hearing damage, and still can induce the disorder of other system, such as nerve system,cardiovascular system and so on. Its effects on blood pressure had attracted widespread attention.Stimulation from various external environments can cause the unbalance of homeostasis in endoplasmic reticulum, which results in endoplasmic reticulum stress. The current study showed that the endoplasmic reticulum stress is closely involved in various cardiovascular diseases, including coronary heart disease, atherosclerosis, etc. Lacidipine is a novel calcium-channel blocker with a continuous and smooth pressure-decreasing effect to protect target organs. It also can relax the blood vessels, improve endothelial function, inhibit smooth muscle proliferation and have anti-atherosclerotic effects. Meanwhile it can significantly reduce cardiovascular events caused by hypertension and mortality rate of cardiovascular disease.As an important antihypertensive drug ,it deserves further application and development.In this study, we made noise stress rat model by breeding rats under noisy condition to observe the changes of blood pressure and endoplasmic reticulum stress in vascular smooth muscle cells of noise stress rats. We measured the media thickness of artery to explore the role and status of the endoplasmic reticulum stress in niose stress rats'vascular remodeling. Meanwhile we explored the effects and mechanism of calcium-channel blocker (CCB) in the prevention and protection niose stress-induced vascular damage.We aimed to clarify molecular mechanisms of vascular damage induced by noise stress and the interventional effects of 1acidipine on it, and to provide new theoretical evidences for prevention and treatment of vascular damage induced by noise stress.MethodsNoise stress rats were used as experiment models in this study. Carotid artery cannulation, Western-blot, immunohistochemistry and other experimental techniques and methods were used to observe: (1) the change of blood pressure in noise stress rats; (2)the changes of the expression of GRP78 and CHOP in vascular smooth muscle cells in niose stress rats; (3) the changes of vascular media thickness in niose stress rats; (4) the effect of CCB on the expression of GRP78 and CHOP and the media thickness of artery.Results(1) Mean arterial blood pressure (MAP) in 4w,6w,8w subgroups (166.90±8.32 mmHg,174.23±8.57mmHg,178.56±9.03mmHg) of the noise group increased progressively during the experiment, and were higher than those in control groups (123.79±8.86mmHg,125.53±9.87mmHg,123.60±9.36mmHg) (P<0.01).(2) Compared with control groups (their OD were 0.47±0.02,0.47±0.03,0.46±0.03),the expression of GRP78 in the subgroups of 4w,6w,8w in the noise group increased significantly (P<0.01).Their optical density OD were 0.65±0.03,0.88±0.04,0.63±0.03.No significant difference (P>0.05) was observed between OD of 2w subgroup in the noise group and 2w subgroup in the control group.OD of the 6w subgroup in the model group was the highest. (3) The expression of CHOP in the subgroups of 4w,6w,8w (their optical density were 0.45±0.05,0.56±0.04,0.67±0.03) in the noise group increased significantly (P<0.05) compared with control group(0.37±0.02,0.39±0.03,0.38±0.02),and that of the 8w subgroup in the noise group was the highest.No significant difference (P>0.05) was observed in OD of 2w subgroup in the noise group compared with that in control group. (4) Compared with control groups (0.27±0.02,0.28±0.03,0.29±0.03),the expression level of GRP78 in the subgroups of 4w,6w,8w in the noise group (0.42±0.03,0.79±0.03,0.45±0.01) increased significantly (P<0.01).No significant difference (P>0.05) was observed between 2w subgroup in the noise group and 2w subgroup in the control group.The expression level of GRP78 of the 6w subgroup in the model group was the highest. (5) The expression level of CHOP in the subgroups of 4w,6w,8w (0.41±0.03,0.58±0.03,0.71±0.03)in the noise group increased significantly (P<0.05) compared with control group (0.13±0.01,0.12±0.02,0.14±0.02), and that of the 8w subgroup in the noise group was the highest. (6) The media thickness of the 6w,8w subgroup (105.89±4.36μm,110.46±5.11μm) in the model group increased significantly compared with control group (93.19±4.32μm,92.67±3.77μm) (P<0.05). In the noise group, the media thickness of the 4w,6w,8w subgroup had significant difference (P<0.01) compared with each other. (7) MAP of the control group,noise group and 1acidipine+noise group were 118.65±9.84mmHg,174.23±6.26mmHg,139.23±8.14mmHg orderly.MAP of the 1acidipine+noise group was lower than the noise group (P<0.01), and higher than the control group (P<0.05). (8) OD representing the expression of GRP78 in the control group,noise group and 1acidipine+noise group were 0.46±0.03,0.87±0.04,0.74±0.04. OD of the 1acidipine+noise group was lower than the noise group (P<0.01), and higher than the control group (P<0.01). (10) Media thickness of the control group,noise group and 1acidipine+noise group was 93.13±4.12μm,105.89±4.36μm,94.56±3.97μm. Media thickness of the noise group was increasing significantly compared with the control group (P<0.01).There was no significant difference between noise group and 1acidipine+noise group (P>0.05) .Conclusion(1) Noise stress can rise blood pressure of rats. (2) Noise can induce endoplasmic reticulum stress in the vascular smooth muscle cells, and subsequently increase the expression of GRP78 and CHOP. (3) Vascular media thickness increased in noise stress rats.This suggested noise can induce vascular remodeling. (3) CCB could inhibit the increased blood pressure, reduce the expression of GRP78 and CHOP in the vascular smooth muscle cells of noise rats,and prevent media thickness increasing. This suggested that CCB could reduce the level of endoplasmic reticulum stress and inhibit vascular remodeling in noise stress rats. |
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