Effects of tetrahydrobiopterin on improve the function of left ventricular diastolic and study its mechanisms in hypertensive mice
10.13699/j.cnki.1001-6821.2018.01.008
- VernacularTitle:四氢生物蝶呤改善高血压小鼠左心室舒张功能的作用及机制研究
- Author:
Ke-Xue LUO
1
;
Jie BIAN
;
Fu-Xing CHEN
Author Information
1. 浙江省立同德医院干部保健科
- Keywords:
tetrahydrobiopterin;
hypertension;
left ventricular diastolic function;
phosphorylated protein kinase B
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(1):30-33
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effects of tetrahydrobiopterin (BH4) on left ventricular diastolic function and expression of phosphorylated protein kinase B (p-Akt) in hypertensive mice.Methods Male C57BL/6 mouse were selected to construct hypertensive models,the mouse modeled successfully were randomly divided into two groups according to their weight:Experimental group (lavage with BH4 solution 10 pL · g-1 · d-1) and model group (lavage with normal saline),20 healthy mouse were selected as sham operation group (lavage with normal saline),at dose of 10 μL · g-I in three groups,all were continuously fed for 7 days.The effect of BH4 intervention on left ventricular function in mice were detected by echocardiography.The expression of Akt and p-Akt proteins in the myocardium were detected by Western blot.Results After BH4 intervention,ratio of left ventricular early diastolic fillig velocity/left ventricular early diastolic mitral annual velocity (E/E')in sham operation group,model group and experimental group were 25.74 ± 5.23,38.45 ± 3.68,32.15 ± 5.24,respectively;the left ventricular end diastolic pressure (LVEDP,mmHg) in the three groups were 84.0 ± 5.2,104.3 ±12.5,100.2±7.5 respectively;the Tau(ms) in the three groups were 10.6 ±0.5,14.3 ±0.8,12.1 ± 0.6,respectively;the end-diastolic pressure-volume relation (EDPVR,mmHg · μL-1) in the three groups were 0.15 ±0.02,0.22 ±0.05,0.16 ±0.05,respectively.The factors in the model group were higher than the sham operation group;while the factors in the experimental group were lower than the model group;the differnce had significantly (P ＜ 0.05 or P ＜ 0.01).There was no significant difference in the expression of Akt protein in each group (P ＞ 0.05).The expression of p-Akt protein in myocardium of experimental group was higher than that of the model group with significantly(P ＜ 0.05).Compared with the model group,the levels of nitric oxide(NO) and superoxide dismutase (SOD) in the myocardial tissue of the experimental group increased and the malonaldehyde (MDA) level decreased with significantly (P ＜ 0.05 or P ＜ 0.01).Conclusion BH4 can decrease the level of myocardial oxidative stress and improve the left ventricular diastolic function by increasing the expression of p-Akt in myocardium of hypertensive mice.
