Effects Of Lecanidipine On Endothelial Function And Autonomic Nervous Activity In Essential Hypertensive Patients

BackgroundEndothelial dysfunction and the injury of autonomic nervous system activity are important pathophysiological progresses in the development of cardiovascular disease, and they are correlated with morbidity and mortality of cardiovascular events. Hypertension is the most common cardiovascular disease in the middle-aged and elderly. Hypertension and its complications, such as heart failure, stroke and renal failure are threatening the lives of patients. Studies have confirmed that endothelial function and autonomic nervous system activity are impaired in hypertensive patients. Therefore, it is conceivable that reversing endothelial dysfunction and autonomic nervous activity could represent an adjunctive target for antihypertensive treatment. Whether lercanidipine is able to improve endothelial function in hypertensive patients has not been reported. It is shown that perindopril can improve endothelial function in essential hypertensive patients. In our study, we observe the effect of lercanidipine on endothelial function in essential hypertensive patients. It is not clear whether lercanidipine or perindopril is able to improve the autonomic nervous system activity. In this study, autonomic nervous system activity parameters (heart rate variability, baroreflex sensitivity, blood pressure variability) were measured at baseline and12weeks later, in order to evaluate whether lercanidipine can improve endothelial function and the effects of lercanidipine and perindopril on autonomic nervous activity.Objective1. To observe whether vascular endothelial function and autonomic nervous system activity are impaired in essential hypertensive patients.2. To observe the correlation between endothelial function and autonomic nervous activity. To observe whether oxidative stress participate the development of endothelial dysfunction and the injury of autonomic nervous activity.3. To observe the effect of lacanidipine on endothelial function.4. To observe the effect of lacanidipine and perindopril on autonomic nervous system activity.5. To compare the effects of the two kinds of anti-hypertension drugs on endothelial function and autonomic nervous activity. Provide the theory of choose anti-hypertension drugs.Methods1. There were63patients of essential hypertension in Zhongshan Hospital, Department of cardiology were enrolled. They are patients with grade Ⅰ or Ⅱ essential hypertension without clinically evident organ demage, and they were never treated or reported a history of discontinued pharmacological antihypertensive treatment and withdrawal over2weeks at least. Patients in hypertensive group were arranged into2groups for12-week treatment with randomly assigned lacanidipine(10-20mg/d), perindopril(4-8mg/d). They are followed up each2weeks.51patients completed the total study. According to a randomized, parallel design,30healthy controls from community enrolled in this study (April2011to January2012).2. We detected brachial artery FMD and nitroglycerin-mediated casodilation (NMD) by high-resodilation between baseline and12-week treatment later. In addition, sitting blood pressure, plasma NO, ET-1, MDA were assessed before and after12-week treatment. Power spectral analysis of HRV, BRS, BPV were used to estimate cardiovascular autonomic function.3. All statistical analyses were performed using SPSS16.0software. All data were expressed as mean±S.D or the median (25th percentile-75th percentile). Qualitative data were analyzed by chi-square test. Continuous variable data between the two groups were compared using independent samples t test or Wilcoxon rank sum test. Paired t-test or wilocoxon rank sum test was used to compare the two groups before and after treatment. Pearson or spearman analysis was used for correlation analysis. P<0.05was considered significant difference.Results1. Vascular endothelial function and autonomic nervous activity in essential hypertensive patients.1.1Mean patient SBP, DBP was elevated compared to normal control (P=0.000). Plasma levels of NO were significantly lower compared to normotensive control(P=0.042), whereas ET-1,MDA levels were significantly higher (P=0.016,0.002). FMD was significantly lower in patients compared to controls (P=0.001) and NMD was similar in both groups(P>0.05). 1.2TV.rri、LF.rri、HF.rri increased in the group of hypertension compared with normotensive control (P=0.020,0.041,0.037), VLF.rri decreased in group of hypertension compared with the control group, but not statistically significant. Total.brs, HF.brs, LF.brs decreased compared with normotensive control (P=0.004,0.029,0.041). TV.bp, LF.bp were were elevated in hypertension group(P=0.019,0.034)2. There are no correlations between the parameters of endothelial function and autonomic nervous system activity.3. Effects of lacanidipine and perindopril on vascular endothelial function, autonomic nervous activity.3.1At baseline, blood pressure, NO, ET-1, MDA, FMD, NMD and parameters of autonomic nervous system activity were similar in in the two treatment groups(P>0.05).3.2Clinical sitting blood pressure in both groups decreased significantly after treatments(P<0.01), but heart rate was no change after lacanidipine and perindopril. At the end of the treatment FMD increased in both groups(P<0.01), Plasma NO and NMD were not changed in both groups. ET-1only decreased in perindopril group(P=0.002). Plasma MDA significantly decreased in both groups(P<0.05).3.3Total.brs, HF.brs significantly increased and TV.bp, LF.bp, HF.bp decreased in both groups (P<0.05)ConclusionEndothelial function and autonomic nervous activity is impaired in hypertensive patients. NO, FMD decreased, ET-1elevated and HRV, BRS decreased, BPV increased in hypertensive patients. There was no correlation between endothelial function and autonomic nervous activity. Like perindopril, Lacanidipine can improve endothelial function. After12-week treatment there was no change of NO in both groups. Lacanidipine and perindopril can improve autonomic nervous activity. There was no difference between the two drugs on the improvement of endothelial function and autonomic nervous system activity.