Folic acid restores endothelial function in ACTH-induced hypertension

Hypertension is associated with increased oxidative stress and vascular endothelium dysfunction. The aim was to study the effect of folic acid (FA) on hypertension, blood nitric oxide (NO), homocysteine (HCY), malondialdehyde (MDA) and reduced glutathione (GSH); aortic tissue glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD); and vascular endothelial function in adrenocorticotrophic hormone (ACTH)-induced hypertension rats. Rats were treated with saline or FA alone (0.04 g/L/day orally, control), or subcutaneous ACTH-induced hypertension (0.2 mg/kg/day, ACTH) groups. Treated FA groups were started before (Folic–ACTH, prevention) and during (ACTH–Folic, reversal) ACTH administrations. Systolic blood pressure (SBP), thymus/body weight ratio, blood urea, creatinine, NO, HCY, MDA and GSH; aortic endothelium-dependent vasodilator (EDD) in response to acetylcholine (ACh), aortic tissue extract for CAT, GPx, and SOD activity; and histopathological changes of aorta and kidney were assessed. Saline or FA alone did not change SBP (P > 0.05). FA, in prevention study, significantly decreased SBP, increased serum NO and GSH, enhanced relaxation response (EDD%) to 1 × 10−4 M ACh; increased aortic tissue GPx, CAT and SOD activity, also revealed nearly normal endothelial cell layer and moderately positive cytoplasmic staining for CD34+ expression versus ACTH-treated rats (P < 0.05). In contrast, FA, in reversal study, did not show significant changes in most of the measured parameters as ACTH-treated group (P > 0.05). FA can be used as an adjuvant therapy for prevention and treatment of ACTH-induced hypertension. The protective role of FA in ACTH-induced hypertension could be attributed via decreasing HCY, MDA (oxidative stress); increasing NO, GSH, GPx, CAT, SOD activity (antioxidants); and restoring endothelial dysfunction.