Response to Treatment of Hyperuricemia in Essential Hypertension
Epidemiologic evidence linking serum uric acid and incident hypertension is rapidly proliferating, and animal models of hyperuricemia have helped elucidate possible mechanisms for this relationship.1 Furthermore, secondary analyses of clinical trial data suggest that the relationship between hypertension treatment and clinical outcomes is related to serum uric acid levels.2,3 The logical next step is to evaluate whether targeting serum uric acid prevents hypertension or hypertension-associated end-organ damage. We agree with Trachtman4 that well-designed, randomized, controlled trials should evaluate the efficacy of uric acid–lowering therapy in the prevention of hypertension.
We also note that the failure of allopurinol to prevent hypertension in spontaneously hypertensive rats does not necessarily contradict the hypothesis that uric acid plays a causal role in human hypertension. As the study by Trachtman et al5 noted, serum uric acid levels do not differ between the spontaneously hypertensive rat and the normotensive Wistar–Kyoto strain. Like most mammals (and in contrast to humans), rats possess the hepatic enzyme uricase, which facilitates the rapid degradation of uric acid. Hyperuricemic rat models of hypertension have used oxonic acid to inhibit uricase, yielding modest elevations in serum uric acid more consistent with those seen in humans.1
Forthcoming studies will address whether uric acid is a viable target for the pharmacological prevention of hypertension in humans. If the results are positive, they will require a careful scrutiny of adverse outcomes, given the potentially broad application of this strategy for the prevention of hypertension.
Watanabe S, Kang DH, Feng L, Nakagawa T, Kanellis J, Lan H, Mazzali M, Johnson RJ. Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity. Hypertension. 2002; 40: 355–360.
Hoieggen A, Alderman MH, Kjeldsen SE, Julius S, Devereux RB, de Faire U, Fyhrquist F, Ibsen H, Kristianson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H, Chen C, Dahlof B. The impact of serum uric acid on cardiovascular outcomes in the LIFE study. Kidney International. 2004; 65: 1041–1049.
Trachtman H. Treatment of hyperuricemia in essential hypertension. Hypertension. 2007; 49: e45.
Trachtman H, Valderrama E, Futterweit S. Nephrotoxicity of allopurinol is enhanced in experimental hypertension. Hypertension. 1991; 17: 194–202.