Effects of xanthine oxidase inhibition with allopurinol on pulse wave velocity depending on antihypertensive therapy

Background Arterial hypertension is commonly associated with hyperuricemia. Numerous clinical studies have shown that xanthine oxidase inhibition improves endothelial function in patients with diabetes, or chronic heart failure smokers. Allopurinol appears to have effect on endothelial function in hypertensives in contrast to uricosuric agents. It is possible that there may be an alternative mechanism by which allopurinol improves arterial wave reflection. One possible mechanism for the action of allopurinol on arterial wave reflection is inhibition of superoxide anion formation and therefore, a reduction in oxidative stress damage to the vascular wall. Recent studies have confirmed that augmentation index (AIx) and pulse pressure amplification correlate with superoxide anion production. Recently, treatment with 300 mg allopurinol for 3 months in patient with hyperuricemia and normal renal function has been shown to lower C-reactive protein levels and blood pressure, and because elevated C-reactive protein levels are associated with increased AIx, it is possible that allopurinol might have affected through an antiinflammatory effect. The aim of our study was to determine the effects of allopurinol on pulse wave velocity depending on angiotensin converting enzyme inhibitor or thiazide therapy. Material and methods The study was carried out in years 2006-2008 in the Department of Hypertension, Angiology and Internal Diseases, University of Medical Sciences in Poznan. Sixty six patients with primary, mild-moderate arterial hypertension diagnosis based on traditional measurements were qualified for research. The patients with suspected or diagnosed secondary hypertension, white-coat hypertension, unstable coronary heart disease, history of myocardial infarction, diabetes and other coexisting chronic illnes were excluded. Patients aged 25 to 70 (mean age 46,17 +/- 10,89) have been studied. Antihypertensive therapy was based on perindopril (n=35) and hydrochlorothiazide (n=31). After 8 weeks of antihypertensive therapy, allopurinol 150 mg daily was added for 2 months. Vitits were conducted in the morning. Following 1-h of rest, blood was withdrawn for measurement of urate, urea, creatinine, glucose, renin acivity, liver function tests, electrolytes, plasma lipids, morphology. Blood pressure was recorded using a validated automated device OMRON 705IT and full clinical history was taken. Ambulatory blood pressure monitoring was made. Twenty-four-hour urate excretion was evaluated. Pulse wave velocity (PWV) was assessed noninvasily, using the validated COMPLIOR analysis system. Measurements were taken at baseline, after 8 of weeks antihypertensive therapy and after next 8 of weeks antihypertensive therapy with allopurinol addition. Results After treatment with allopurinol, PWV decreased from 11,13 +/- 1,64to10,22 +/- 1,40 m/s (Delta-0,91). The mean PWV in P group, after allopurinol treatment, decreased from 10,74 +/- 1,45 m/s to 10,02 +/- 1,21 m/s (p=0,00008), in H group PWV decreased from 11,58 +/- 1,74 m/s to 10,44 +/- 1,59 m/s (p=0,00002). Conclusions 1. Allopurinol treatment significantly reduced pulse wave velocity regardless of the type of antihypertensive therapy. 2. In spite of no significant changes in blood pressure after allopurinol treatment, effect of allopurinol therapy on pulse wave velocity corelated with changes of systolic blood pressure and pulse pressure. 3. Allopurinol reduces uric acid concentration regardless of the type of antihypertensive therapy.