Vitamin K1 attenuates hypoxia-induced relaxation of rat carotid artery.
Vascular responses to hypoxia are heterogeneous and involve the release of vasodilators substances such as nitric oxide (NO) and prostacyclin (PGI(2)). In vitro studies have shown that Vitamin K(1) modulates the release of arachidonic acid (AA) in vascular cells, and thus inhibits the capacity of blood vessels to synthesise vasodilator AA metabolites. The aim of our work was to investigate the effects of Vitamin K(1) on the hypoxia-induced vasorelaxation. Hypoxia was induced by changing the gas from 95% O(2)/5% CO(2) to a mixture containing 95% N(2)/5% CO(2). Rat carotid arteries were pre-contracted with phenylephrine (Phe, 10(-8)mol/l) and when the contraction reached a plateau, the bath was bubbled with 95% N(2)/5% CO(2) for 15 min. In intact rings, there was a total relaxation after 15 min of exposure to hypoxia. Removal of the endothelium strongly reduced hypoxia-induced relaxation. In intact rings, indomethacin and L-NAME reduced the hypoxic relaxation after 5 min of exposure but not after 10 or 15 min. Exposure of endothelium-intact rings to Vitamin K(1) (5 x 10(-6) and 5 x 10(-5)mol/l), L-NAME+indomethacin as well as the combination of L-NAME+indomethacin+Vitamin K(1) reduced the hypoxic relaxation after 5 and 10 min of exposure but not after 15 min. At 5 x 10(-7)mol/l Vitamin K(1) did not attenuate hypoxia-induced relaxation. It was also found that Vitamin K(1) (5 x 10(-6) and 5 x 10(-5)mol/l) inhibited ACh-induced relaxation in normoxic conditions. These results show that the effect of Vitamin K(1) on attenuating hypoxia-induced vasorelaxation is concentration-dependent and probably related to its action on endothelial cells.
Tirapelli
Carlos R
CR
Department of Pharmacology, Faculty of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
Mingatto
Fábio E
FE
De Godoy
Márcio A F
MA
Ferreira
Rosemary
R
De Oliviera
Ana M
AM
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D010837:Vitamin K 1 / Q000494:pharmacology*
D010837:Vitamin K 1