title: Vitamin K requirement in Danish anticoagulant-resistant Norway rats (Rattus norvegicus).
abstract: Resistance to warfarin has been connected to an increase in dietary requirement for vitamin K in British strains of the Norway rat, Rattus norvegicus (Berk). This study examines vitamin K requirement of Danish anticoagulant-resistant Norway rats using a vitamin K deficient feeding test. Wild bromadiolone-resistant rats sampled from different localities in Denmark and rats from bromadiolone-resistant and susceptible laboratory strains were fed on a vitamin K deficient diet over a maximum period of 15 days. Development of vitamin K deficiency, measured as reduced blood-clotting capacity, took place in 43% of the Danish resistant rats and was independent of sex, treatment with supplementary vitamin K3 and sampling locality. Development of deficiency was slower for resistant rats that were supplemented with vitamin K3 prior to the feeding test, suggesting storage of the vitamin K in a vitamin body pool. Intraperitoneal administration of vitamin K1 revealed that 80 microg vitamin K1 kg(-1) bodyweight was sufficient to restore normal blood clotting activity in deficient rats, while 60 microg vitamin K1 kg(-1) bodyweight was insufficient. We conclude that vitamin K requirement is moderately increased in Danish homozygous resistant rats whereas heterozygous resistant rats only have a minor increase in vitamin K requirement compared with susceptible rats. We found no indication of different resistance types being present in our test material since vitamin K requirement was not different between rats from separate sampling localities.
authors.affiliation: Danish Pest Infestation Laboratory, Skovbrynet 14, DK-2800 Kongens Lyngby, Denmark. ssl@ssl.dk
authors.forename: Mette D K
authors.initials: MD
authors.lastname: Markussen
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Heiberg
authors.forename: Robert
authors.initials: R
authors.lastname: Nielsen
authors.forename: Herwig
authors.initials: H
authors.lastname: Leirs
mesh_terms: D015110:4-Hydroxycoumarins / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D004351:Drug Resistance; D005260:Female; D008297:Male; D051381:Rats; D014812:Vitamin K / Q000494:pharmacology*; D014813:Vitamin K Deficiency / Q000503:physiopathology; D014859:Warfarin / Q000494:pharmacology*
chemical_list: D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D014812:Vitamin K; D014859:Warfarin; C021636:bromadiolone