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