TY - JOUR
T1 - Folic acid does not limit endothelial dysfunction induced by ischemia and reperfusion
T2 - A human study
AU - Dragoni, Saverio
AU - Gori, Tommaso
AU - Di Stolfo, Giuseppe
AU - Sicuro, Silvia
AU - Forconi, Sandra
AU - Parker, John D.
PY - 2005/10
Y1 - 2005/10
N2 - Nitric oxide synthase (NOS) uncoupling is a condition of increased production of superoxide anion associated with a decreased production of nitric oxide (NO) by this enzyme. Folic acid can prevent and/or reverse NOS uncoupling in the setting of diabetes, smoking, hypercholesterolemia, and nitrate tolerance. Whereas animal studies showed a protective effect of folic acid in ischemia and reperfusion (IR) injury, no study tested whether folic acid administration limits IR-induced endothelial dysfunction in humans. In a double-blind, parallel study, 20 healthy young male volunteers were randomized to receive folic acid, 10 mg/d for 7 days, or matching placebo. At the end of the treatment period, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR injury (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference at baseline between groups in any variable. In the placebo group, IR significantly blunted FMD (before IR, 6.7 ± 1.0%; after IR, 1.5 ± 1.3%, P <0.01). A similar effect was observed in the folic acid group (before IR, 6.3 ± 1.1%; after IR, 2.1 ± 1.0%, P = ns compared with placebo). As opposed to animal studies, high-dose folic acid does not protect the vascular endothelium from IR injury in humans.
AB - Nitric oxide synthase (NOS) uncoupling is a condition of increased production of superoxide anion associated with a decreased production of nitric oxide (NO) by this enzyme. Folic acid can prevent and/or reverse NOS uncoupling in the setting of diabetes, smoking, hypercholesterolemia, and nitrate tolerance. Whereas animal studies showed a protective effect of folic acid in ischemia and reperfusion (IR) injury, no study tested whether folic acid administration limits IR-induced endothelial dysfunction in humans. In a double-blind, parallel study, 20 healthy young male volunteers were randomized to receive folic acid, 10 mg/d for 7 days, or matching placebo. At the end of the treatment period, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR injury (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference at baseline between groups in any variable. In the placebo group, IR significantly blunted FMD (before IR, 6.7 ± 1.0%; after IR, 1.5 ± 1.3%, P <0.01). A similar effect was observed in the folic acid group (before IR, 6.3 ± 1.1%; after IR, 2.1 ± 1.0%, P = ns compared with placebo). As opposed to animal studies, high-dose folic acid does not protect the vascular endothelium from IR injury in humans.
KW - Folic acid
KW - Ischemia-reperfusion injury
KW - Nitric oxide synthase
UR - http://www.scopus.com/inward/record.url?scp=26044452063&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=26044452063&partnerID=8YFLogxK
U2 - 10.1097/01.fjc.0000177983.68563.d1
DO - 10.1097/01.fjc.0000177983.68563.d1
M3 - Article
C2 - 16160603
AN - SCOPUS:26044452063
VL - 46
SP - 494
EP - 497
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 4
ER -