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.