"These results are the first to show that treatment with allopurinol can improve vessel dilation in heart failure patients," says Allan D. Struthers, M.D., F.R.C.P., coauthor of the study.

In the placebo-controlled, double-blind crossover study, the British researchers randomized 11 patients with mild to moderate heart failure to either allopurinol or placebo daily for one month. Researchers gave each subject a short-acting form of acetylcholine and measured dilation response. Next, they crossed-over each participant to either allopurinol or placebo and repeated the experiment. They discovered that treatment with allopurinol increased average forearm blood flow nearly 50 percent more than use of placebo, says Struthers.

The researchers also administered two drugs that induce vascular dilation independent of the endothelium. In both cases, the drugs worked roughly equivalently in subjects receiving allopurinol and in patients receiving placebo---further evidence that allopurinol works on the endothelium.

"Allopurinol is thought to work by blocking the action of xanthine oxidase, which produces the superoxide that promotes oxidative stress," Struthers says. "Much of the previous work on reducing free radicals has focused on using antioxidant vitamins to negate their effect. This represents an alternate strategy of preventing the formation of oxygen-free radicals."

It is also possible the drug reduces concentrations of uric acid, the causative agent in gout. Earlier studies have shown an association between mortality and uric acid concentration, he says. Uric acid concentrations fell nearly 60 percent in patients taking allopurinol, even though their levels were in the normal range at baseline, he says.

"We cannot tell from this study, whether allopurinol produced its benefit by way of decreasing superoxide anions or decreasing uric acid or both," he says.

Struthers' says similar results have been found in patients with diabetes and high cholesterol levels, two other conditions associated with high levels of free radicals.

In an accompanying editorial, Ulf Landmesser, M.D., and Helmut Drexler, M.D., professors at Medical School Hannover (Germany), praised the work saying, "If this concept holds true and can be confirmed in a larger patient population -- it could pave the way to an inexpensive and possibly effective addition to the treatment of patients with chronic heart failure."