Folic acid prevented and reversed adrenocorticotropic hormone-induced hypertension in the rats

Abstract

Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is accompanied by increased oxidative stress1 and decreased nitric oxide (NO) production.2 Folic acid decreases reactive oxidant species production and increases production of tetrahydrobiopterin (BH4), an important co-factor for the formation of nitric oxide. The aim of this study was to investigate the effect of folic acid on blood pressure in Sprague-Dawley (SD) rats treated with ACTH. Male SD rats (n=10 in each group) were treated with saline or ACTH (0.2mg/kg/day s.c.) for 11 days in a prevention study and 13 days in a reversal study. Folic acid (0.04 g/L in drinking water) was given 4 days prior to and during ACTH treatment (prevention study). In the reversal study, ACTH/saline was administered daily for 13 days and from day 8 (T8), rats were co-administered folic acid daily for 5 days. Systolic blood pressure (SBP) was measured by the tail-cuff method. Thymus wet weight/body weight (BW) ratio was measured as a marker of glucocorticoid activity. Results were expressed as mean±SEM. SBP of saline treated rats was unchanged. ACTH increased SBP (from 106±4 to 131±5 mmHg, P<0.001). Folic acid alone did not affect SBP, but folic acid prevented ACTH-induced hypertension (SBP 130±4 ACTH vs 110±1 mmHg ACTH+Folate T10, P’<0.01). Folic acid given from T8 reversed ACTH-induced hypertension (from134±1 T8 to 116±2 mmHg T12, P<0.002). Thymus weight/BW ratio decreased significantly in ACTH treated rats (saline 168.6±11 and ACTH 52.1±11 mg/100g BW, P<0.0001). Folic acid alone did not affect thymus weight/BW ratio. Thus, folic acid prevented and reversed ACTH-induced hypertension in the SD rat. Given previous data showing L-arginine also prevents3 and reverses4 ACTH-induced hypertension, folic acid is unlikely to be acting through increased BH4 production, and may be exerting its effect as an antioxidant.