Interaction of hypoxanthine/xanthine oxidase with nitrergic relaxation in the porcine gastric fundus.
The influence of hypoxanthine (HX)/xanthine oxidase (XO) on short-term [electrical field stimulation (EFS; 4 Hz) for 10 s and 3 min; bolus of exogenous NO (10(-5) M)] and long-term [EFS (4 Hz) and continuous NO-infusion for 20 min] nitrergic relaxations was investigated in circular muscle strips of the pig gastric fundus. HX (3x10(-4) M) / XO (64 mu ml(-1)) did not affect EFS for 10 s and 3 min; the short-lasting relaxation in response to a bolus of exogenous NO (10(-5) M) was changed into a biphasic relaxation with a small and short first phase followed by a larger and prolonged second phase. Cu/Zn superoxide dismutase (Cu/Zn SOD; 1000 u ml(-1)) and uricase (100 mu ml(-1)) respectively enhanced the amplitude of the first phase and diminished the amplitude of the second phase. Ascorbate (5x10(-4) M) and bilirubin (2x10(-4) M) prevented the prolonged component. Exposure to HX/XO during long-term EFS elicited a complete, stable reversal of relaxation starting after a delay. During continuous NO-infusion, HX/XO induced an immediate, complete but transient reversal. The antioxidants bilirubin, ascorbate, alpha-tocopherol, urate, glutathione and Cu/Zn SOD, the hydrogen peroxide degrading enzyme catalase, the hydroxyl radical scavengers dimethylsulphoxide and mannitol, and the cofactor flavin adenine dinucleotide did not influence the reversal induced by HX/XO during either EFS or NO-infusion. The cell-permeable manganese SOD mimetic EUK-8 modified the stable reversal during long-term EFS into a transient one. The results suggest that a nitrated uric acid derivative is responsible for the prolonged second phase in the relaxation to a bolus of exogenous NO in the presence of HX/XO. The exact underlying mechanism of the reversal induced by HX/XO during sustained relaxation remains unclear.
Colpaert
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EE
Heymans Institute of Pharmacology, Ghent University Medical School, De Pintelaan 185, B-9000 Ghent, Belgium.
Lefebvre
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RA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016166:Free Radical Scavengers; D005748:Gastric Fundus / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology; D009130:Muscle, Smooth / Q000201:enzymology / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D013552:Swine; D014503:Urate Oxidase / Q000502:physiology; D014527:Uric Acid / Q000378:metabolism; D014969:Xanthine Oxidase / Q000502:physiology*
D000975:Antioxidants; D016166:Free Radical Scavengers; D014527:Uric Acid; D009569:Nitric Oxide; D014969:Xanthine Oxidase; D014503:Urate Oxidase