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[多沙唑嗪与可溶性鸟苷酸环化酶在大鼠高血压模型中的作用]

[Doxazosin and soluble guanylate cyclase in a rat model of hypertension].

作者信息

Rodríguez-Feo J A, Gómez J, Núñez A, Rico L, Fortes J, de Andrés R, Cabestrero F, Farré J, Casado S, López-Farré A

机构信息

Laboratorio de Investigación Cardiovascular e Hipertensión. Fundación Jiménez Díaz, Madrid, Spain.

出版信息

Rev Esp Cardiol. 2001 Jul;54(7):880-6.

PMID:11446964
Abstract

BACKGROUND

Although different studies have evaluated the ability of endothelial cells to produce NO in the setting of the endothelial dysfunction associated with hypertension, less it is known about the soluble guanylate cyclase system.

AIM

To analyze the level of expression of sGC in the vascular wall in Stroke-prone spontaneously hypertensive rats (SHRSP). Moreover, the effect of treatment with an alpha1 adrenergic antagonist, doxazosin, on sGC expression was also evaluated.

METHODS

The study was performed in 24 untreated 20-week-old SPSHR and 12 SPSHR treated orally with doxazosin (10 mg/Kg bw/day; for 15 days). A group of normotensive Wistar-Kyoto (WKY) rats were used as controls (n = 12).

RESULTS

Isolated aortic segments from SHRSP showed impaired response to SNP. Doxazosin treatment prevented impaired vasodilatory response to SNP. Expression of the beta1 sGC in the vascular wall of SHRSP determined by Western blot and immunohistochemistry was markedly reduced with respect to that of WKY. Doxazosin treatment increased of beta1 sGC expression in treated SHRSP particularly at the medium level with respect to that of untreated SHRSP.

CONCLUSION

SHRSP showed reduced expression of beta1 sGC in the vascular wall and an impaired vasodilator response to SNP which improved with doxazosin treatment. These results suggest the role the sGC system may play in the global treatment of endothelial dysfunction.

摘要

背景

尽管不同研究已评估了在内皮功能障碍(与高血压相关)情况下内皮细胞产生一氧化氮的能力,但对于可溶性鸟苷酸环化酶系统的了解较少。

目的

分析易卒中型自发性高血压大鼠(SHRSP)血管壁中可溶性鸟苷酸环化酶(sGC)的表达水平。此外,还评估了用α1肾上腺素能拮抗剂多沙唑嗪治疗对sGC表达的影响。

方法

该研究对24只未经治疗的20周龄SHRSP和12只经口服多沙唑嗪治疗(10 mg/kg体重/天;持续15天)的SHRSP进行。一组正常血压的Wistar-Kyoto(WKY)大鼠用作对照(n = 12)。

结果

SHRSP分离的主动脉段对硝普钠(SNP)的反应受损。多沙唑嗪治疗可预防对SNP的血管舒张反应受损。通过蛋白质印迹法和免疫组织化学测定,SHRSP血管壁中β1 sGC的表达相对于WKY大鼠明显降低。多沙唑嗪治疗可增加治疗组SHRSP中β1 sGC的表达,尤其是相对于未治疗的SHRSP,在中层水平增加。

结论

SHRSP显示血管壁中β1 sGC表达降低,对SNP的血管舒张反应受损,而多沙唑嗪治疗可改善这种情况。这些结果表明sGC系统可能在内皮功能障碍的整体治疗中发挥作用。

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Rev Esp Cardiol. 2001 Jul;54(7):880-6.
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