| Objective:To investigate the relationship between plasma Asymmetric dimethylarginine (ADMA)and Homocysteine(Hcy) in essential hypertention and speculate whether ADMA,Hey are independent risk factors. To understand the internal relationship of ADMA,Hcy,NO and eNOS as well as the blood pressure and its grade in essential hypertension after the administration of folic acid,vitamin B12 and probucol to explore new risk factors, incidence mechanism and preventive measures.Methods:Using case-control study method, a total of 120 subjects diagnosed essential hypertension were randomly divided into three groups. Among the first group we gave only anti-hypertensive therapy, and the second group on the basis of treatment of the first group were given folic acid and VitB12 (folate:5mg Qd; VitB12:50ug, Bid). The third group on the basis of treatment of the first group were given folic acid,VitB12 and probucol(500mg, Bid). Additionally,30 cases of healthy people were selected as control group. Observe changes of ADMA,Hcy,NO and eNOS among the baseline,2 weeks and 12 weeks.Results:1.Plasma ADMA concentration (0.23±0.11μmol/L),Hey concentration (22.45±14.30μmol/L) in patients with essential hypertension were both significantly higher than the concentration of the control group (0.13±0.06μmol/L),(13.61±6.29μmol/L), the differences were both significant (P＜0.01); Serum NO concentration (65.51±13.87μmol/L),eNOS concentration (21.13±4.80ng/ml) were both significantly lower than the concentration of the control group (77.27±9.19μmol/L),(29.27±3.77ng/ml), the differences were both significant (P<0.01).2.In the group of essential hypertension, ADMA concentration (0.24±0.13μmol/L) of male patients was higher than female patients (0.23±0.11μmol/L)(P>0.05); Hcy concentration of male patients(26.66±15.82μmol/L) was higher than female patients (20.34±13.08μmol/L), the difference was statistically significant (P＜0.01). In the control group, ADMA concentration of female patients (0.14±0.07μmol/L) was higher than male patients (0.11±0.03μmol/L)(P>0.05); plasma Hcy concentration of male patients (16.70±5.95μmol/L) was higher than female patients (11.54±5.77μmol/L), the difference was significant (P<0.05).3.The comparasion among the various indicators to classification of hypertension in essential hypertension:with the increase of classification of hypertension, plasma ADMA concentration was elevated gradully, but there was no significant difference; the plasma Hcy concentration gradually increased, the plasma Hcy concentrations of patients with hypertension grade 2 or grade 3 was higher than patients with hypertension grade 1 (P<0.01), but there were no significant differences in Hcy concentrations beween grade 2 and grade 3; serum NO concentration increased with the increase of classification of hypertension, and serum NO concentration of patients with hypertension grade 3 was significantly lower than the grade 1(P<0.05); serum eNOS concentrations increased with the increase of classification of hypertension, however, there were no significant differences.4.Patients with hypertension complicated with hyperlipemia ADMA concentration (0.23±0.13μmol/L),Hcy concentration (24.57±17.95μmol/L) were both higher than those with simple hypertension ADMA(0.20±0.10μmol/L) and Hcy(23.15±14.85μmol/L) of the concentration(P<0.05),and NO concentration (56.14±14.39μmol/L) was significantly lower than those with the simple hypertension group (67.12±15.94μmol/L) of the concentration (P<0.01).5.The comparasion in group during treatment in essential hypertension:in the first group plasma ADMA,Hcy and serum NO,eNOS concentrations had not significantly differences(P>0.05); in the second group plasma ADMA. Hcy concentrations decreased gradually during treatment of 12 weeks, ADMA,Hcy concentrations were significantly lower than the baseline after the treatment of 12 weeks(P<0.05); serum NO,eNOS concentrations were significantly higher than the baseline(P<0.05); in the third group plasma ADMA,Hcy concentrations decreased and serum NO,eNOS concentrations increased gradually during treatment of 12 weeks. And comparing with the baseline, AD MA,Hey concentrations decreased and the serum NO,eNOS concentrations increased gradually after 2 weeks(P<0.05); after 12 weeks ADMA,Hey concentrations were significantly lower than the baseline(P<0.01), and serum NO,eNOS concentrations were significantly higher than the baseline(P<0.01).6.The comparasion among groups in essential hypertension during treatment:in the second group ADMA,Hcy,NO,eNOS concentrations were not significant changes comparing with the first group after the treatment for 2 weeks(P<0.05); ADMA, Hey concentrations were lower than the first group after the treatment for 12 weeks(P<0.01), and NO,eNOS concentrations were higher significantly than the first group(P<0.01); in the third group ADMA,Hey concentrations were lower than the first and the second group after the treatment for 2 weeks, and NO,eNOS levels was higher significantly than the first and second group(P<0.05);ADMA,Hey concentrations were even lower than the first and second group after the treatment for 12 weeks(P<0.01), and NO,eNOS concentrations were even higher significantly than the first and second group(P<0.01).7.In the group of essential hypertension ADMA were positive correlations with Hey (r=0.546),smoking(r=0.205)(P<0.05), and were negative correlations with eNOS (r=-0.557),NO (r=-0.538)(P<0.05). Hey were positive correlations with smoking (r= 0.363),SBP (r=0.457),DBP (r= 0.382) (P＜0.05), and were negative correlations with eNOS (r=-0.524), NO (r=-0.546) (P<0.05). In the control of age,TG and other risk factors, the partial correlation analysis showed that ADMA was positively correlated with Hey.8. Logistic regression analysis showed that ADMA,Hey were respectively potential risk factor for hypertension.Conclusions:1.The elevation of ADMA,Hey concentrations and the reduction of NO,eNOS concentrations suggested that ADMA and Hey may be involved in the pathophysiology of hypertension and may play a role in endothelial dysfunction. 2. With the grade of hypertension increased, plasma ADMA,Hey concentrations increased gradully, NO,eNOS concentrations decreased gradully, suggesting that the higher concentrations could lead to the more severe endothelial dysfunction arteriolosclerosis.3.Patients with hypertension complicated with hyperlipemia ADMA,Hey concentrations were higher than those with the simple hypertension, and NO concentration was significantly lower than those with the simple hypertension, suggesting that the patients could lead to the more severe endothelial dysfunction than those with the single hypertension by ADMA,Hey.4. In the control of other risk factors, the partial correlation analysis showed that ADMA was positively correlated with Hey. ADMA,Hey were negative correlations with NO,eNOS. And suggeste that Hey may affect endothelial function and increase small arteriosclerosis, also promote the development of hypertension by ADMA. And Logistic regression analysis showed that ADMA,Hey were respectively potential risk factor for hypertension.5.The patients given folic acid (5mg, Qd),VitB12(50ug, Bid) for 12 weeks significantly decreased plasma ADMA,Hey levels, elevated serum NO,eNOS levels; The patients given folic acid,VitB12 and Probucol(500mg, Bid) more significantly decreased plasma ADMA,Hey levels and elevated serum NO,eNOS levels after 2 weeks. The patients given folic acid,VitB12 and Probucol for 2 weeks had the similar effects with the patients given folic acid,VitB12 for12 weeks. In the third group the levels of ADMA,Hey can be reduced to the levels of healthy people, NO,eNOS levels could rise to healthy people after 12 weeks. The right suplyment of folic acid,VitB12 and/or probucol may help improve endothelial function and inhibit the vicious circle by the reduction of ADMA and Hey, slowing the progress of atherosclerosis and prevention of cardiovascular events in patients with hypertension.
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