Effects of the xanthine oxidase system on cardiac function in anaesthetised rats.
This investigation aimed to determine whether contractile dysfunction of the myocardium could be produced upon generation of free radicals in the anaesthetised rat. The enzyme xanthine oxidase, combined with its substrate purine and an iron source, was used to generate free radicals in the venous circulation. The suspended form of xanthine oxidase, with substrate, produced a transient, significant depression in the contractile indices dP dt-1 max and dP dt-1 P-1 and arterial blood pressure, 1146 +/- 87 mm Hg s-1, 9 +/- 1 s-1, and 18 +/- 1 mm Hg, respectively. This could not be attenuated by the enzymatic free radical scavengers superoxide dismutase and catalase. Furthermore, the suspended xanthine oxidase alone or its vehicle were able to produce a similar effect to that of the complete free-radical-generating system. The maximum soluble dose of the crystalline form of the enzyme when employed in the generating system had no effect upon administration despite its production of superoxide radicals in vitro. These results suggest that the haemodynamic effects of the free-radical-generating system containing the suspended form of xanthine oxidase were due to the effects of its vehicle and that the free-radical-generating system containing the crystalline form of the enzyme did not produce sufficient free radicals in vivo to modify myocardial contractility.
Laycock
S K
SK
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
McMurray
J
J
Kane
K A
KA
Parratt
J R
JR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D002712:Chlorides; D003460:Crystallization; D003574:Cytochrome c Group / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D005609:Free Radicals; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010084:Oxidation-Reduction; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism / Q000494:pharmacology*
D002712:Chlorides; D003574:Cytochrome c Group; D005290:Ferric Compounds; D005609:Free Radicals; D011687:Purines; D004492:Edetic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; C024555:ferric chloride