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Uric acid as radical scavenger and antioxidant in the heart

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Abstract

Uric acid (UA) is released from the heart of many species, including man, and its site of formation has been shown to be the microvascular endothelium. Since UA reacts with oxygen radicals in vitro, experiments were conducted on guinea pig hearts perfused with Krebs-Henseleit buffer (KHB) to evaluate whether the formation of UA could afford protection from damage by radicals and oxidants. The following results were obtained: (1) Upon addition of the hydroxyl radical scavenger DMSO to the perfusate, the coronary rate of release of endogenous uric acid was increased relative to the precursor purines. (2) UA was degraded during passage through the coronary system and also in KHB in vitro after addition of substances generating hydroxyl radicals or hypochlorite. Superoxide (O −2 ) radicals did not seem to react directly with UA, though UA concentration-dependently quenched the chemiluminescence generated from luminol in the presence of O −2 and OH radicals. (3) Coronary dilatation by acetylcholine (Ach) and sub-μM concentrations of adenosine, induced by both via endothelial mechanisms, was attenuated after prolonged inhibition of endothelial UA formation by allopurinol. Furthermore, the effect of Ach but not of adenosine proved acutely sensitive to methylene blue and O −2 , substances known to inactivate EDRF. This finding suggests involvement of EDRF in Ach-mediated, but not in adenosine-induced dilatation of the intact coronary system. Exogenously applied UA prevented the impairment of vascular responses to Ach and adenosine caused by allopurinol, and to Ach upon generation of O −2 .(4) Hearts performed more pressure-volume work and exhibited greater functional stability when perfused with KHB supplemented with UA in a physiological concentration. It is concluded that uric acid can actually serve as a physiologic radical scavenger and antioxidant, maintaining functional responsiveness of the coronary system and of the myocardium.

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Authors and Affiliations

  1. Department of Physiology, University of Munich, Pettenkoferstrasse 12, D-8000, München, Federal Republic of Germany

    B. F. Becker, N. Reinholz, T. Özçelik, B. Leipert & E. Gerlach

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  1. B. F. Becker
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  2. N. Reinholz
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  3. T. Özçelik
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  4. B. Leipert
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  5. E. Gerlach
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Additional information

A preliminary report has been given at the Joint Meeting of the Deutsche Physiologische Gesellschaft and the Physiological Society, 16–19 March 1988, in Würzburg, Germany [6]

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Becker, B.F., Reinholz, N., Özçelik, T. et al. Uric acid as radical scavenger and antioxidant in the heart. Pflügers Arch 415, 127–135 (1989). https://doi.org/10.1007/BF00370582

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  • DOI: https://doi.org/10.1007/BF00370582

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