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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)304-10
Number of pages7
JournalAmerican Journal of Hypertension
Volume20
Issue number3
DOIs
Publication statusPublished - 2007
Externally publishedYes

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Folic Acid
Glucocorticoids
Dexamethasone
Hypertension
Adrenocorticotropic Hormone
Blood Pressure
Biopterin
Isoprostanes
Homocysteine
Serum
Drinking
Sprague Dawley Rats
Pressure

Cite this

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. / Folic acid prevents and partially reverses glucocorticoid-induced hypertension in the rat. In: American Journal of Hypertension. 2007 ; Vol. 20, No. 3. pp. 304-10.
@article{a30ea6c3a41f4eca9ea640a512a3dd6b,
title = "Folic acid prevents and partially reverses glucocorticoid-induced hypertension in the rat",
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.",
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author = "Yuchun Miao and Yi Zhang and Lim, {Pek S} and Yada Kanjanapan and Mori, {Trevor A} and Croft, {Kevin D} and John Earl and Lee, {Sze Y} and McKenzie, {Katja U S} and Lexian Hu and Whitworth, {Judith A}",
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Miao, Y, Zhang, Y, Lim, PS, Kanjanapan, Y, Mori, TA, Croft, KD, Earl, J, Lee, SY, McKenzie, KUS, Hu, L & Whitworth, JA 2007, 'Folic acid prevents and partially reverses glucocorticoid-induced hypertension in the rat', American Journal of Hypertension, vol. 20, no. 3, pp. 304-10. https://doi.org/10.1016/j.amjhyper.2006.08.007

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

In: American Journal of Hypertension, Vol. 20, No. 3, 2007, p. 304-10.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Folic acid prevents and partially reverses glucocorticoid-induced hypertension in the rat

AU - Miao, Yuchun

AU - Zhang, Yi

AU - Lim, Pek S

AU - Kanjanapan, Yada

AU - Mori, Trevor A

AU - Croft, Kevin D

AU - Earl, John

AU - Lee, Sze Y

AU - McKenzie, Katja U S

AU - Hu, Lexian

AU - Whitworth, Judith A

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - Adrenocorticotropic Hormone

KW - Animals

KW - Antihypertensive Agents/blood

KW - Biopterin/analogs & derivatives

KW - Blood Pressure/drug effects

KW - Body Weight/drug effects

KW - Dexamethasone

KW - Disease Models, Animal

KW - F2-Isoprostanes/blood

KW - Folic Acid/blood

KW - Glucocorticoids

KW - Homocysteine/blood

KW - Hypertension/blood

KW - Male

KW - Nitric Oxide/blood

KW - Rats

KW - Rats, Sprague-Dawley

KW - Thymus Gland/drug effects

KW - Time Factors

U2 - 10.1016/j.amjhyper.2006.08.007

DO - 10.1016/j.amjhyper.2006.08.007

M3 - Article

VL - 20

SP - 304

EP - 310

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 3

ER -