C. Cardillo et al., XANTHINE-OXIDASE INHIBITION WITH OXYPURINOL IMPROVES ENDOTHELIAL VASODILATOR FUNCTION IN HYPERCHOLESTEROLEMIC BUT NOT IN HYPERTENSIVE PATIENTS, Hypertension, 30(1), 1997, pp. 57-63
Hypercholesterolemic and hypertensive patients have impaired endotheli
um-dependent vasorelaxation because of decreased nitric oxide activity
, but the mechanism underlying this abnormality is unknown. This study
sought to determine whether an increased breakdown of nitric oxide by
xanthine oxidase-generated superoxide anions could participate in the
se forms of endothelial dysfunction. We studied vascular responses to
intrabrachial infusion of acetylcholine (an endothelium-dependent vaso
dilator, 7.5 to 30 mu g/min) and sodium nitroprusside (a direct smooth
muscle dilator, 0.8 to 3.2 mu g/min) by strain-gauge plethysmography
before and during the combined administration of oxypurinol (300 mu g/
min), a xanthine oxidase inhibitor, in 20 hypercholesterolemic patient
s, 20 essential hypertensive patients, and 20 normal subjects. The vas
odilator response to acetylcholine was blunted in hypercholesterolemic
(highest flow, 8.2+/-8 mL.min(-1).dL(-1)) and hypertensive (8.5+/-4 m
L.min(-1).dL(-1)) patients compared with control subjects (13.8+/-6.6
mL.min(-1).dL(-1)) (both P<.001); however, no differences were observe
d in the response to sodium nitroprusside. Oxypurinol did not change t
he response to acetylcholine in control subjects (P=.26) and improved,
but did not normalize, its vasodilator effect in hypercholesterolemic
patients (P<.01). Oxypurinol did not affect the response to acetylcho
line in hypertensive patients (P=.34) and did not modify the response
to sodium nitroprusside in any group. These results suggest that xanth
ine oxidase-generated superoxide anions are partly responsible for the
impaired endothelial vasodilator function of hypercholesterolemic pat
ients. In contrast, this mechanism does not appear to play a significa
nt role in essential hypertension.