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NITRIC OXIDE‐DEPENDENT ENDOTHELIAL FUNCTION IS UNAFFECTED BY ALLOPURINOL IN HYPERCHOLESTEROLAEMIC SUBJECTS
Author(s) -
O’Driscoll JG,
Green DJ,
Rankin JM,
Taylor RR
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03125.x
Subject(s) - allopurinol , dilator , sodium nitroprusside , xanthine oxidase inhibitor , endothelial dysfunction , vasodilation , medicine , pharmacology , endocrinology , nitric oxide , endothelium , xanthine oxidase , chemistry , biochemistry , enzyme
SUMMARY 1. Hypercholesterolaemia is associated with abnormal endothelium‐related vasodilator function, possibly due to increased destruction •NO by superoxide anions (•O 2 – ). Oxypurinol, a xanthine oxidase (XO) inhibitor with anti‐oxidant properties and the active metabolite of the commonly used drug allopurinol, 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 allopurinol improves •NO dilator function in hypercholesterolaemic subjects. 3. A randomized double‐blind, placebo‐controlled cross‐over design evaluated the effect of allopurinol (300 mg daily for 4 weeks) on forearm blood flow (FBF) responses to intrabrachial infusion of acetylcholine (ACh), sodium nitroprusside (SNP) and N G ‐monomethyl‐ L ‐arginine ( L ‐NMMA) in nine hypercholesterolaemic subjects. 4. Endothelium‐dependent vascular responses to ACh and L ‐NMMA were not significantly altered by allopurinol. The endothelium‐independent vasodilator response to SNP was similarly unchanged. 5. These results indicate that allopurinol does not influence basal or stimulated activity of the •NO dilator system in hypercholesterolaemic subjects. If intracellular •O 2 – inactivation •NO is responsible for endothelial dysfunction in hypercholesterolaemia, the source may be other than XO dependent. However, generation of •O 2 – during the conversion of allopurinol to oxypurinol could offer an alternative, and probably more likely, explanation for the ineffectiveness of allopurinol in vivo .