叶酸可预防并部分逆转大鼠糖皮质激素诱导的高血压。

Folic acid prevents and partially reverses glucocorticoid-induced hypertension in the rat.

作者信息

Miao Yuchun, Zhang Yi, Lim Pek S, Kanjanapan Yada, Mori Trevor A, Croft Kevin D, Earl John, Lee Sze Y, McKenzie Katja U S, Hu Lexian, Whitworth Judith A

机构信息

High Blood Pressure Research Unit, John Curtin School of Medical Research, Australian National University, Canberra, Australia.

出版信息

Am J Hypertens. 2007 Mar;20(3):304-10. doi: 10.1016/j.amjhyper.2006.08.007.

DOI:10.1016/j.amjhyper.2006.08.007

PMID:17324744

Abstract

BACKGROUND

To investigate the effect of folic acid on the increased pressure in rats treated with either adrenocorticotropic hormone (ACTH) or dexamethasone (Dex), and to further investigate the role of tetrahydrobiopterin (BH(4)) in any effect of folic acid by comparing the effect of BH(4) with that of folic acid in Dex hypertension.

METHODS

Male Sprague-Dawley (SD) rats were treated with saline, subcutaneous ACTH (0.2 mg/kg/d) or Dex (10 microg/rat/d). Folic acid (0.04 g/L drinking) or BH(4) (10 mg/kg/d intraperitoneally) was started before (prevention) and during (reversal) glucocorticoid treatment.

RESULTS

Saline, BH(4), vehicle for BH(4), or folic acid alone did not change systolic blood pressure (BP). Systolic BP was increased by ACTH and Dex. Folic acid, but not BH(4), prevented the development of hypertension caused by ACTH and Dex treatment. The ACTH and Dex hypertension were partially reversed by folic acid. The BH(4) increased plasma total biopterin concentrations. The Dex decreased plasma NOx concentrations but had no effect on plasma biopterin concentrations. The ACTH and Dex increased plasma F(2)-isoprostane concentrations and decreased serum homocysteine concentrations compared with control but had no effect on serum folate concentrations. Folic acid increased serum folate concentrations compared with control but had no effect on homocysteine concentrations.

CONCLUSIONS

Folic acid prevented and partially reversed both ACTH and Dex hypertension in rats without modifying the increase in plasma F(2)-isoprostane concentrations. Given that BH(4) failed to prevent ACTH or Dex hypertension, folic acid is unlikely to be acting through increased BH(4) production. The precise mechanism for the BP-lowering effect of folic acid in this model of hypertension remains to be determined.

摘要

背景

研究叶酸对用促肾上腺皮质激素（ACTH）或地塞米松（Dex）处理的大鼠血压升高的影响，并通过比较四氢生物蝶呤（BH₄）与叶酸在Dex高血压中的作用，进一步研究BH₄在叶酸任何作用中的角色。

方法

雄性Sprague-Dawley（SD）大鼠用生理盐水、皮下注射ACTH（0.2mg/kg/d）或Dex（10μg/大鼠/d）处理。在糖皮质激素治疗前（预防）和治疗期间（逆转）开始给予叶酸（0.04g/L饮水）或BH₄（10mg/kg/d腹腔注射）。

结果

生理盐水、BH₄、BH₄的溶剂或单独的叶酸均未改变收缩压（BP）。ACTH和Dex使收缩压升高。叶酸而非BH₄可预防ACTH和Dex治疗所致高血压的发生。ACTH和Dex高血压可被叶酸部分逆转。BH₄可增加血浆总生物蝶呤浓度。Dex可降低血浆NOx浓度，但对血浆生物蝶呤浓度无影响。与对照组相比，ACTH和Dex可增加血浆F₂-异前列腺素浓度并降低血清同型半胱氨酸浓度，但对血清叶酸浓度无影响。与对照组相比，叶酸可增加血清叶酸浓度，但对同型半胱氨酸浓度无影响。