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螺内酯对自发性高血压大鼠血管外膜诱导型一氧化氮合酶活性的影响 被引量:3

Effect of spironolactone on L-arginine/iNOS/NO pathway of aortic adventitia in spontaneously hypertensive rats
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摘要 目的观察醛固酮受体拮抗剂螺内酯干预自发性高血压大鼠(SHR)对血管外膜诱导型一氧化氮合酶(iNOS)的影响,探讨醛固酮在血管损伤性疾病中的作用及机制。方法10周龄雄性SHR大鼠20只,分成2组:螺内酯组(10只,20mg·kg^-1·d^-1螺内酯灌胃)和对照SHR组(10只,等量自来水灌胃),10周龄雄性WKY大鼠10只作为正常对照组(等量自来水灌胃),共干预6周。各组均于干预前后每周测1次尾动脉收缩压。6周后处死,取主动脉,测定血管外膜L-精氨酸(L—Arg)摄取、iNOS活性(^3H-瓜氨酸生成法)及NOx含量(Griess法测定)。结果对照SHR组血管外膜iNOS活性[(12.55±2.27)pmol·mg^-1·min^-1]、[^3H]-L—Arg摄取[(0.88±0.19)nmol·mg^-1·min^-1]及NOx含量[(2.07±0.39)μmol/L]较对照WKY组[分别为(5.96±1.87)pmol·mg^-1·min^-1,(0.51±0.15)nmol·mg^-1·min^-1(1.55±0.32)μmol/L,均P〈0.01]显著增高,与对照SHR组比较,螺内酯组血管外膜iNOS活性[(8.32±1.84)pmol·mg^-1·min^-1]、[^3H]-L-Arg摄取[(0.61±0.15)nmol·mg^-1·min^-1]和NOx含量[(1.64±0.27)μmol/L]显著下降(均P〈0.01)。结论螺内酯能够抑制SHR血管外膜L—Arg—iNOS—NO系统。醛固酮参与血管外膜L—Arg—iNOS—NO通路的激活,这种激活除了通过参与血压升高间接发挥作用外,可能还具有直接作用。 Objective Adventitia plays an important role in vascular injury diseases. Nitric oxide (NO) from inducible nitric oxide synthase (iNOS) is involved in many cardiovascular diseases, iNOS/NO pathway is activated in aorta of spontaneously hypertensive rats (SHRs). The role of aldosterone in Larginine (L-Arg) /iNOS/NO pathway of aortic adventitia is uncertain. We investigated the effect of aldosterone antagonist spironolaetone on adventitial L-Arg/iNOS/NO pathway in SHRs. Methods Twenty male SHR(10 weeks old, 220-280 g) were randomly divided into 2 groups (10 in each): untreated or treated with the aldosterone receptor antagonist, spironolactone (20 mg/kg per day) for 6 weeks. Agematched Wistar-Kyoto rats (WKY) were used as control. Systolic blood pressure ( tail-cuff method) was measured weekly. Six weeks later, the rats were sacrificed. The whole aorta was collected and aortic adventitia was isolated, iNOS activity, [ ^3H ]-L-Arg transport assay of aortic adventitia were carried out by isotope-labeled L-arginine conversion rate measurement, and measurement of nitrate/nitrite (NOx) , an index of NO production of aortic adventitia was assayed with the Griess reaction. Results iNOS activity, [^ 3 H ] -L-Arg transport and NO production were greatly increased in aortic adventitia of SHR[ (12. 55 ± 2. 27 ) pmol · ^-1 mg ^-1 min^-1 , (0. 88 ±0. 19) pmol ·mg^-1 · min^-1 and(2. 07 ±0. 39) μmol/L) ] compare versus WKY [ (5.96 ±1.87 ) pmol ·mg^-1 · min^-1 ( 0. 51 ± 0. 15 ) pmol ·mg^-1 · min^-1and ( 1.55 ± 0. 32 ) μmol/L, P 〈 0. 01 ], and decreased significantly by spironolaetone treatment [ ( 8. 32 ± 1.84 ) pmol ·mg^-1 · min^-1 (0. 61±0. 15) pmol ·mg^-1 · min^-1 and (1.64 ±0.27) μmol/L, P 〈0.01 ]. Conclusion L-Arg/iNOS/ NO is activated in aortic adventitia of SHR. Spironolactone can inhibit the activation of L-Arg/iNOS/NO pathway. Aldosterone may play an important role in some cardiovascular diseases such as atheroscler
出处 《中华医学杂志》 CAS CSCD 北大核心 2010年第6期424-426,共3页 National Medical Journal of China
关键词 螺内酯 一氧化氮合酶 一氧化氮 Spironolactone Nitric oxide synthase Nitric oxide
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