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Glutathione administration prevents oxygen radical induced lipid peroxidation in isolated rabbit hearts
Pharmacological Research, W
160
TISSUE SELECTIVITY
OF REC 15/2375
26, Supplement 1, 1992
IN ISOLATED SMOOTH AND CARDIAC MllSCLES
Marina Ibba, Patrizia Angelico, Luciano Guarneri & Rodolfo Pharmacological Department, Recordati S.p.A., Milan0 (Italy)
Testa
Ret 15/2375 is a new dihydropyridine calcium antagonist with marked antihypertensive activity (1). In the present study, we examined its in vitro calcium antagonistic activity on isolated rat smooth muscles colon and bladder contracted by KC1 80 mM), in comparison to (aorta, nitrendipine and its in vitro effects on cardiac inotropism (rabbit to nitrendipine ventricular strip electrically stimulated) in comparison and felodipine. Ret 15/2375 produced a potent relaxant On rat aorta, effect with an IC50 value of 1.3x10-10 M. The compound exerted also a relaxant effect on bladder and colon preparations, but at concentrations respectively 180 and 10 times higher than on aorta tissue. Nitrendipine proved practically equiactive on the three tissues examined. Ret 15/2375 showed a negative inotropic effect at concentrations higher than nitrendipine and felodipine, with 1~50 values of 1.2x10-5, 1.4x10-8 and 1.8x10-8 M respectively. These results provide evidence that Ret 15/2375 is endowed with enhanced selectivity for vascular versus the other studied smooth muscles. By comparing the potency in inhibiting electrically-evoked responses of ventricular strips and responses to K+ in spiral strips of aorta, Ret 15/2375 showed a remarkably high vascular selectivity. (1) Drugs Rut., 1987, 12: 1113-Ibid 1989, 14: 1226-Ibid 1991, 16: 1144.
GLUTATHIONE ADMINISTRATION PREVENTS OXYGEN RADICAL INDUCED LIPID PEROXIDATION IN ISOLATED RABBIT HEARTS. Isabella Tritto, Giuseppe Ambrosio, Pietro Paolo Elia, Annalisa Scognamiglio,Massimo Chiariello. Division of Cardiology, 2nd School of Medicine, University of Naples, Italy. Ox gen free radicals are hi hly reactive species that can induce oxidative alterations of many ccl Kular components. Mem %rane lipids have been shown to be a preferential target, via peroxidative chain reaction with final formation of malonyldialdeh de (MDA). Oxidation of mtracellular reduced glutathione (GSH) to its oxidized form (G 8 SC) is one of the main defense systems against oxygen radicals. However, it has not been directly assessedwhether exogenous administration of glutathione can prevent oxygen radical damage in intact organs. To test this hypothesis, Langendorff perfused rabbit hearts were exposed toexo enous ox radicals generated by the purine/xanthine oxidase system (P/X0: 2.3 mM an8 100 mU Ben ml, respectively) for 5 min, followed by 30 min recovery (n=7); treated hearts received GSH (1 mM) during P/X0 infusion (n=6). At the end of the experiments, the left ventricles were homogenized and centrifuged to evaluate lipid peroxidation in the whole homogenate as well as in subcellular fractions. MDA levels were measured as nMoles/mg of protein (data are expressed as mean + SEM; * = Whole homogenate Mitocondrial fraction Lysosomal fraction Cytosolic fraction Thus, infusion of GSH prevented peroxidation of membrane lipids in subcellular organelles of hearts exposed to oxygen radicals. Our data indicate that GSH treatment may prevent tissue damage induced by oxygen radicals in isolated hearts.
160
TISSUE SELECTIVITY
OF REC 15/2375
26, Supplement 1, 1992
IN ISOLATED SMOOTH AND CARDIAC MllSCLES
Marina Ibba, Patrizia Angelico, Luciano Guarneri & Rodolfo Pharmacological Department, Recordati S.p.A., Milan0 (Italy)
Testa
Ret 15/2375 is a new dihydropyridine calcium antagonist with marked antihypertensive activity (1). In the present study, we examined its in vitro calcium antagonistic activity on isolated rat smooth muscles colon and bladder contracted by KC1 80 mM), in comparison to (aorta, nitrendipine and its in vitro effects on cardiac inotropism (rabbit to nitrendipine ventricular strip electrically stimulated) in comparison and felodipine. Ret 15/2375 produced a potent relaxant On rat aorta, effect with an IC50 value of 1.3x10-10 M. The compound exerted also a relaxant effect on bladder and colon preparations, but at concentrations respectively 180 and 10 times higher than on aorta tissue. Nitrendipine proved practically equiactive on the three tissues examined. Ret 15/2375 showed a negative inotropic effect at concentrations higher than nitrendipine and felodipine, with 1~50 values of 1.2x10-5, 1.4x10-8 and 1.8x10-8 M respectively. These results provide evidence that Ret 15/2375 is endowed with enhanced selectivity for vascular versus the other studied smooth muscles. By comparing the potency in inhibiting electrically-evoked responses of ventricular strips and responses to K+ in spiral strips of aorta, Ret 15/2375 showed a remarkably high vascular selectivity. (1) Drugs Rut., 1987, 12: 1113-Ibid 1989, 14: 1226-Ibid 1991, 16: 1144.
GLUTATHIONE ADMINISTRATION PREVENTS OXYGEN RADICAL INDUCED LIPID PEROXIDATION IN ISOLATED RABBIT HEARTS. Isabella Tritto, Giuseppe Ambrosio, Pietro Paolo Elia, Annalisa Scognamiglio,Massimo Chiariello. Division of Cardiology, 2nd School of Medicine, University of Naples, Italy. Ox gen free radicals are hi hly reactive species that can induce oxidative alterations of many ccl Kular components. Mem %rane lipids have been shown to be a preferential target, via peroxidative chain reaction with final formation of malonyldialdeh de (MDA). Oxidation of mtracellular reduced glutathione (GSH) to its oxidized form (G 8 SC) is one of the main defense systems against oxygen radicals. However, it has not been directly assessedwhether exogenous administration of glutathione can prevent oxygen radical damage in intact organs. To test this hypothesis, Langendorff perfused rabbit hearts were exposed toexo enous ox radicals generated by the purine/xanthine oxidase system (P/X0: 2.3 mM an8 100 mU Ben ml, respectively) for 5 min, followed by 30 min recovery (n=7); treated hearts received GSH (1 mM) during P/X0 infusion (n=6). At the end of the experiments, the left ventricles were homogenized and centrifuged to evaluate lipid peroxidation in the whole homogenate as well as in subcellular fractions. MDA levels were measured as nMoles/mg of protein (data are expressed as mean + SEM; * = Whole homogenate Mitocondrial fraction Lysosomal fraction Cytosolic fraction Thus, infusion of GSH prevented peroxidation of membrane lipids in subcellular organelles of hearts exposed to oxygen radicals. Our data indicate that GSH treatment may prevent tissue damage induced by oxygen radicals in isolated hearts.