The catecholamine-mediated positive inotropic effect of simple quinones is related to superoxide anion generation.
In guinea pig and rat cardiac tissue, redox cycling benzoquinones (2,5-dimethyl-p-benzoquinone and duroquinone) and naphthoquinones (menadione and 2,3-dimethoxy-1,4-naphthoquinone) generated superoxide anion (O2-.) both through one- and two-electron reductions, the generation being significantly greater in guinea pig than in rat tissue. In electrically driven left atria isolated from guinea pig and rat, menadione and 2,5-dimethyl-p-benzoquinone but not duroquinone caused a concentration-dependent positive inotropic effect. Unlike guinea pig, 2,3-dimethoxy-1,4-naphthoquinone had no effect in rat tissue. Naphthoquinones and 2,5-dimethyl-p-benzoquinone were more active in guinea pig than in rat tissue, their effect being dependent on the release of catecholamines from adrenergic stores. A linear relationship (r = 0.90) between the amount of O2-. generated by benzo- and naphthoquinones in guinea pig and rat heart and the extent of catecholamine-dependent positive inotropic effect was evident. An amount of O2-. higher than 600 nmol/g of tissue per min was calculated to be necessary to determine the catecholamine-mediated increase in contractility. Lipid peroxidation was not involved in quinone-induced catecholamine release.
Floreani
M
M
Department of Pharmacology, University of Padova, Italy.
Carpenedo
F
F
D000818:Animals; D016275:Atrial Function; D016227:Benzoquinones / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D053138:Cyclohexenes; D005609:Free Radicals; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D013481:Superoxides / Q000378:metabolism*; D014812:Vitamin K / Q000494:pharmacology
D016227:Benzoquinones; D002395:Catecholamines; D053138:Cyclohexenes; D005609:Free Radicals; D009285:Naphthoquinones; D013481:Superoxides; D014812:Vitamin K; C020617:2,5-dimethyl-4-benzoquinone; C063002:2,3-dimethoxy-1,4-naphthoquinone; C034257:duroquinone