TABLE 4

Effects of XO inhibitors on vascular dysfunction associated with hypercholesterolemia, atherosclerosis, hypertension, diabetes, and chronic heart failure


Model

Disease or Trigger

Mode of XO Inhibition

Effects of XO Inhibition

Reference
Rabbit Hypercholesterolemia Oxypurinol Decreased vascular free radical production Ohara et al. (1993); Mugge et al. (1994); White et al. (1996)
Human (60 patients) Hypercholesterolemia and hypertension Oxypurinol Oxypurinol improved in vivo endothelial-dependent vasorelaxation in hypercholesterolemic but not hypertensive patients Cardillo et al. (1997)
Rat HHcy-induced by methhionine feeding Oxypurinol Impaired flow-mediated vascular responses of HHcy arterioles were prevented by oxypurinol Bagi et al. (2002)
Rat SHRs N.A. Increased XO activity in the hearts of hypertensive rats Janssen et al. (1993)
Rat SHRs Tungsten Increased XO activities in the mesenteric tissues of SHRs, and normalization of endothelial function and blood pressure in these animals after inhibition of XO activity by tungsten Suzuki et al. (1998)
Rat SHRs Oxypurinol Significantly higher uric acid levels in SHRs than in normal rats; oxypurinol decreased the blood pressure in SHRs but not in normal rats Nakazono et al. (1991)
Rat Dahl salt-sensitive hypertensive rats Tungsten Tungsten-rich diet lowered blood pressure in Dahl salt-sensitive hypertensive rats but not in salt-resistant rats Swei et al. (1999)
Rat SHRs Allopurinol Renal XO activity was increased and correlated with systolic blood pressure during growth in SHRs but not in WKY rats; allopurinol had a negligible effect on blood pressure but prevented hypertension-induced left ventricular and renal hypertrophy in SHRs Laakso et al. (1998, 2004)
Rat Oxonic acid-induced hypertension Allopurinol Allopurinol or uricosuric agent (benziodarone) prevented uricase inhibitor (oxonic acid)-induced hypertension Mazzali et al. (2001)
Rat Hypertensive double-transgenic rats harboring human renin and angiotensinogen genes (dTGR) Oxypurinol Preincubation with oxypurinol improved impaired endothelium-dependent vascular relaxation in rats with elevated angiotensin II levels Mervaala et al. (2001)
Rat Dexamethasone-induced hypertension Allopurinol Allopurinol reduced blood pressure in hypertensive rats and attenuated the increased XO levels in cremaster muscle Wallwork et al. (2003)
Human (19 and 11 patients) CHF Allopurinol Allopurinol improved endothelial function Doehner et al. (2002); Farquharson et al. (2002)
Human (24 patients) CHF N.A. Endothelium-bound xanthine-oxidase activity was increased by >200% in patients with CHF and inversely correlated with endothelium-dependent vasodilation Landmesser et al. (2002)
Human (32 patients)
Hyperuricemia-induced
Allopurinol
3-month therapy with allopurinol improved impaired endothelium-dependent flow-mediated dilation in hyperuricemic subjects
Mercuro et al. (2004)
  • N.A., not available; HHcy, hyperhomocysteinemia; WKY, Wistar-Kyoto.