Zhong X, Liang G, He Z
Respiratory Department, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2000 Dec;23(12):727-9.
To investigate the protective and therapeutic effects of pinacidil on hypoxia-induced pulmonary hypertension(HPH) and pulmonary vascular remodeling.
46 male Wister rats were divided into control group, hypoxic group and treated group (hypoxic rat treated with pinacidil for 4 weeks). Rat models with chronic HPH were established by chronic hypobaric hypoxia [(10 +/- 0.5)% O2, 4 weeks)]. The mean pulmonary arterial pressure (mPAP) and right ventricle/left ventricle and septum [RV/(LV + S)] were measured and the small pulmonary arterial morphologic changes were observed with morphmetric analysis under microscopes in three groups.
(1) The level of mPAP(28.4 +/- 2.8) mm Hg and RV/(LV + S) (0.30 +/- 0.03) were significantly higher in the hypoxic group than (16.2 +/- 1.8) mm Hg and (0.22 +/- 0.03) in control group respectively (P < 0.01). Morphometry investigation showed that the external diameter became smaller and that ratio of vascular wall thickness to external diameter (MT%) (25.7 +/- 2.6)% and ratio of vascular wall area to total area (MA%) (75.3 +/- 5.6)% significantly increased in the hypoxic group. (2) The mPAP(23.3 +/- 2.6) mm Hg, RV/(LV + S) (0.27 +/- 0.04) and pulmonary vascular pathologic changes MT%(22.1 +/- 2.5)% and MA% (67.0 +/- 6.1)% significantly decreased in the treated group, indicating that pinacidil inhibited HPH and hypoxia-induced thickening and muscularization of small pulmonary arteria.
Pinacidil may partly prevent the development of HPH and pulmonary vascular remodeling.
探讨吡那地尔对缺氧性肺动脉高压(HPH)及肺血管重塑的保护和治疗作用。
将46只雄性Wistar大鼠分为对照组、缺氧组和治疗组(用吡那地尔治疗4周的缺氧大鼠)。通过慢性低压缺氧[(10±0.5)%O₂,4周]建立慢性HPH大鼠模型。测量三组大鼠的平均肺动脉压(mPAP)及右心室/左心室和室间隔[RV/(LV+S)],并在显微镜下用形态计量分析观察小肺动脉的形态学变化。
(1)缺氧组的mPAP水平(28.4±2.8)mmHg及RV/(LV+S)(0.30±0.03)显著高于对照组的(16.2±1.8)mmHg及(0.22±0.03)(P<0.01)。形态计量学研究显示,缺氧组小肺动脉外径变小,血管壁厚度与外径之比(MT%)(25.7±2.6)%及血管壁面积与总面积之比(MA%)(75.3±5.6)%显著增加。(2)治疗组的mPAP(23.3±2.6)mmHg、RV/(LV+S)(0.27±0.04)及肺血管病理变化MT%(22.1±2.5)%和MA%(67.0±6.1)%显著降低,表明吡那地尔可抑制HPH及缺氧诱导的小肺动脉增厚和肌化。
吡那地尔可能部分预防HPH的发展及肺血管重塑。