Zhong X, Liang G, He Z
Department of Respiratory Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Zhonghua Nei Ke Za Zhi. 2001 Aug;40(8):525-8.
To investigate the roles of the vascular endothelial growth factor(VEGF) and endothelin-1(ET-1) in pulmonary vascular remodelling in rats with hypoxia-induced pulmonary hypertension(HPH) and the effect of pinacidil on VEGF and ET-1 in rats with HPH.
46 male Wister rats were divided into three groups i.e. control group, hypoxic group and treated group (hypoxic rats treated with pinacidil for 4 weeks). Rat models with chronic HPH were established by chronic hypobaric hypoxia [(10.0 +/- 0.5)% O2, 4 weeks]. The levels of VEGF and ET-1 in serum and the mean pulmonary arterial pressure (mPAP) and the weight ratio of right ventricle (RV)/left ventricle and septum (LV + S) [RV/(LV + S)] were measured and the small pulmonary arterial morphologic changes were observed with morphometric analysis under microscopes in the three groups.
(1) The levels of VEGF[(118.73 +/- 55.40) ng/L] and ET-1[(221.2 +/- 56.2) ng/L] in serum, mPAP [(28.4 +/- 2.8) mm Hg, 1 mm Hg = 0.133 kPa] and RV/(LV + S) (0.296 +/- 0.033) were significantly higher in the hypoxic group than those in the control group (P < 0.01). Morphometry showed that the external diameter of the small pulmonary arteries became smaller and the ratio of vascular wall thickness to external diameter (MT%) (25.70 +/- 2.58)% and ratio of vascular wall area to total area (MA%) (75.300 +/- 5.600)% significantly increased in the hypoxic group. (2) The levels of VEGF[(78.20 +/- 16.45) ng/L] and ET-1[(181.6 +/- 30.5) ng/L] in serum, mPAP[(23.3 +/- 2.6) mm Hg], RV/(LV + S) (0.266 +/- 0.037), MT%(22.10 +/- 2.51)% and MA% (66.900 +/- 0.061)% significantly decreased in the treated group.
VEGF and ET-1 play important roles in the development of HPH and pulmonary vascular remodelling. Pinacidil may partly inhibit the development of HPH and pulmonary vascular remodelling by decreasing VEGF and ET-1.
探讨血管内皮生长因子（VEGF）和内皮素-1（ET-1）在低氧性肺动脉高压（HPH）大鼠肺血管重塑中的作用以及吡那地尔对HPH大鼠VEGF和ET-1的影响。
46只雄性Wistar大鼠分为三组，即对照组、低氧组和治疗组（低氧大鼠用吡那地尔治疗4周）。通过慢性低压低氧[（10.0±0.5）%O₂，4周]建立慢性HPH大鼠模型。检测三组大鼠血清中VEGF和ET-1水平、平均肺动脉压（mPAP）以及右心室重量与左心室加室间隔重量之比[RV/（LV+S）]，并在显微镜下用形态计量学分析观察小肺动脉形态学变化。
（1）低氧组血清中VEGF[（118.73±55.40）ng/L]和ET-1[（221.2±56.2）ng/L]水平、mPAP[（28.4±2.8）mmHg，1mmHg=0.133kPa]以及RV/（LV+S）（0.296±0.033）均显著高于对照组（P<0.01）。形态计量学显示，低氧组小肺动脉外径变小，血管壁厚度与外径之比（MT%）（25.70±2.58）%以及血管壁面积与总面积之比（MA%）（75.300±5.600）%显著增加。（2）治疗组血清中VEGF[（78.20±16.45）ng/L]和ET-1[（181.6±30.5）ng/L]水平、mPAP[（23.3±2.6）mmHg]、RV/（LV+S）（0.266±0.037）、MT%（22.10±2.51）%以及MA%（66.900±0.061）%均显著降低。
VEGF和ET-1在HPH的发生发展及肺血管重塑中起重要作用。吡那地尔可能通过降低VEGF和ET-1部分抑制HPH的发生发展及肺血管重塑。
