| BackgroundWith the improvement of people's living standard and the increase of working stress, the incidence rate of essential hypertension(EH) has been increased year by year, so it becomes important to early detect and prevent the development of EH, EH's complications and target organ dysfunction. Recent studies show that in the early stage of EH, there are some vascular structural and functional changes, and endothelial dysfunction, decreased large artery distensibility and atherosclerosis are involved in the development of hypertension.In the past, the coronary endothelial function was detected by infusing acetylcholine to the coronary artery, but this method was invasive and had low repeatability, so was not used widely among the majority of hypertensive patients. For the detection of arterial buffering function, the classical index is pulse wave velocity (PWV), but this method is affected easily by the cooperation of the patients and needs long time. The researches about assessing the vascular structural changes or atherosclerosis are mainly by a relatively direct method of arterial stenosis level, which is detected through angiography. As we know, angiography is invasive, less repeatable and only observes vascular lumens. In recent years, it was found that ultrasound detection of brachial artery flow-mediated dilation (FMD) was correlated with vascular endothelial function. The ultrasound detection of large artery's compliance and (or) dilatancy changes may be earlier than orthodox PWV. The ultrasound detection of periph arterial intima-medial thickness (IMT) and coronary atherosclerosis has well dependability. Ultrasonic testing of above-mentioned indexs is simple, non-invasive and has the characteristics of repeatable strong and more cost-effective. So in recent years, scholars have begun to use ultrasound to study vascular endothelial function and the buffering function, and through the carotid artery intima-media thickness to predict the changes degree of coronary atherosclerosis.Manidipine was developed by WuTian drug industry in Japan and first licensed to clinical use in 1990. It is a novel dihydropyridine calcium channel blocker, which has inhibitory action on L-type as well as N-type calcium channels. Manidipine could selectively block the smooth muscle cell's calcium channel, so as to dilate vessels, reduce the peripheral vascular resistance and arterial blood pressure. In clinical studies, Manidipine was showed to act smoothly and lastingly, and have high selectivity, so it can effectively reduce blood pressure but do not increase heart rate, and decrease the proteinuria in diabetic patients. However, it is unclear whether Manidipine could improve the vascular endothelial function and structure in patients with HT, and whether Manidipine could delay progression of atherosclerosis. Objectives1. To observe the change of blood vessel function and common carotid artery intima-media thickness in patients with hypertension, so as to provide the new method to detect the progression of hypertension exactly and early.2. To evaluate effects of Manidipine on the changes of vascular function and carotid artery IMT in the patients with hypertension.Methods35 healthy subjects as control group; 60 patients with mild to moderate essential hypertension after a 1-2 week placebo run-in period, were treated with Manidipine for 8 weeks. Vascular ultrasound was carried out at the end of placebo period and active treatment period, recording the common carotid artery IMT, the diameter at diastole telophase(D0 and D1)before and after pressurizing hyperemia, the diameter at deflation telophase(Ds)and diastole telophase (Dd)of brachial artery, ascending aorta and common carotid artery. Then we calculated the changing rate of D0, D1,Ds and Dd, the cross-sectional compliance (CSC), volumic distensibility (VD), Peterson's elastic modulus (Ep), stiffness index (β) of brachial artery, ascending aorta and common carotid artery.Results1. Clinical characteristics of hypertension group and control group:there were 95 cases recruited in the study. Among of them,60 patients were patients with hypertension, and 35 cases are healthy adults. The two groups matched well at the following parameters:age, body mass index, heart rate, and gender ratio (p>0.05). The pressure in the hypertension group was significantly higher than that in the control group, (147.73±10.12/98.28±85.27mmHg vs 117.31±7.53/75.54±4.47 mmHg,p<0.01);2. The comparison of vascular function between the hypertension group and control group:ΔD%, CSC, and VD of brachial artery parameter in the hypertension group were significantly lower than those in the control group (all p<0.01), but the Ep and (3 of the hypertension group are significantly higher than those of the control group (all p<0.01). Ascending artery parameters such as CSC and VD of the hypertension group were significantly lower than those of the control group (all p <0.01), but the Ep andβof the hypertension group are significantly higher than those of the control group (all p<0.01); Carotid artery has the same result (all p<0.01);3. The comparison of common carotid artery IMT between the hypertension group and control group:The common carotid artery IMT in the hypertension group was significantly thicker than that in the control group (0.75±0.14mm vs 0.56±0.10mm,p<0.01);4. The effect of Manidipine on the blood pressure and heart rate:After Manidipine treatment of 8 weeks, the SBP, DBP, PP and MAP were decreased significantly (p<0.01), while the heart rate had no significant change (p>0.05);5. The effect of Manidipine on blood vessel function:After Manidipine treatment of 8 weeks,ΔD%, CSC, and VD of brachial artery parameter were significantly increased (all p<0.01), while the Ep andβwere notably decreased (all p<0.01). After treatment, the CSD and VD of ascending artery were significantly increased (all p<0.01), but Ep andβsignificantly decreased. The results of CSC, VD and Ep in common carotid artery were similar with ascending artery(all p<0.01), but theβhad no significant decrease (p>0.05);6. The effect of Manidipine on common carotid artery IMT:After Manidipine treatment of 8 weeks, the IMT of common carotid artery was decreased, but the change had no statistical difference (0.74±0.16mm vs 0.75±0.14mm,p>0.05).Conclusions1. The change in vascular function of the patients with hypertension is earlier than the vascular structure, so we can early find the development of hypertension by detecting the vascular function. It is a valuable, simple and reliable method to detect the vascular function and structure;2. Manidipine has the antihypertensive effect which are lasting and smooth, but it does not increase the heart rate. Manidipine is effective in improving the vascular endothelial function and the great arterial buffering function, and improving the vascular structure to a certain extent.
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