Nitric oxide-dependent endothelial function is unaffected by allopurinol in hypercholesterolaemic subjects

1. Hypercholesterolaemia is associated with abnormal endothelium-related va sodilator function, possibly due to increased destruction . NO by superoxid e anions (. O-2(-)). Oxypurinol, a xanthine oxidase (XO) inhibitor with ant i-oxidant properties and the active metabolite of the commonly used drug al lopurinol, reduces . NO quenching in vitro and has been reported to acutely improve endothelial function in hypercholesterolaemic subjects. 2. The purpose of the present study was to determine whether oral allopurin ol improves . NO dilator function in hypercholesterolaemic subjects. 3. A randomized double-blind, placebo-controlled cross-over design evaluate d the effect of allopurinol (300 mg daily for 4 weeks) on forearm blood flo w (FBF) responses to intrabrachial infusion of acetylcholine (ACh), sodium nitroprusside (SNP) and N-G-monomethyl-L-arginine (L-NMMA) in nine hypercho lesterolaemic subjects. 4. Endothelium-dependent vascular responses to ACh and L-NMMA were not sign ificantly altered by allopurinol, The endothelium-independent vasodilator r esponse to SNP was similarly unchanged. 5. These results indicate that allopurinol does not influence basal or stim ulated activity of the . NO dilator system in hypercholesterolaemic subject s. If intracellular . O-2(-) inactivation . NO is responsible for endotheli al dysfunction in hypercholesterolaemia, the source may be other than XO de pendent. However, generation of . O-2(-) during the conversion of allopurin ol to oxypurinol could offer an alternative, and probably more likely, expl anation for the ineffectiveness of allopurinol in vivo.