Folic acid prevents and partially reverses glucocorticoid-induced hypertension in the rat.
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.
Miao
Yuchun
Y
High Blood Pressure Research Unit, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Zhang
Yi
Y
Lim
Pek S
PS
Kanjanapan
Yada
Y
Mori
Trevor A
TA
Croft
Kevin D
KD
Earl
John
J
Lee
Sze Y
SY
McKenzie
Katja U S
KU
Hu
Lexian
L
Whitworth
Judith A
JA
D000324:Adrenocorticotropic Hormone; D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone; D004195:Disease Models, Animal; D028441:F2-Isoprostanes / Q000097:blood; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids; D006710:Homocysteine / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000187:drug effects; D013997:Time Factors
D000959:Antihypertensive Agents; D028441:F2-Isoprostanes; D005938:Glucocorticoids; D006710:Homocysteine; D001708:Biopterins; D009569:Nitric Oxide; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D005492:Folic Acid; C003402:sapropterin