Vitamin K(1) prevents the effect of hypoxia on phenylephrine-induced contraction in the carotid artery.
The purpose of the present study was to investigate the effects of vitamin K(1) on vascular smooth muscle contractility in response to phenylephrine (Phe) during hypoxia. Rat carotid rings were placed in an organ chamber containing Krebs' solution. The rings were subjected to hypoxia by changing the gas from 95% O(2):5% CO(2) to a mixture containing 95% N(2):5% CO(2). Concentration response curves for Phe were determined before, during, and after exposure to hypoxia. Endothelium-intact rings were incubated with vitamin K(1) for 10 min in normoxic conditions before being subjected to hypoxia. In another set of experiments, endothelium-intact rings were incubated with N(G)-nitro-L-arginine methyl ester (L-NAME), indomethacin or a combination of these drugs for 30 min. In endothelium-intact rings, hypoxia caused significant reductions in E(max) (from 0.97 +/- 0.03 to 0.61 +/- 0.04 g/mg; mean +/- SEM) and pD(2) values (from 8.26 +/- 0.07 to 7.67 +/- 0.10). Removal of a functional endothelium effectively prevented the hypoxia-induced reduction in E(max) values, but not in pD(2) values (from 9.14 +/- 0.10 to 8.70 +/- 0.11). Pretreatment with vitamin K(1) at 3 concentrations (5 x 10(-8), 5 x 10(-7), 5 x 10(-6) mol/l) prevented the inhibitory effect of hypoxia in intact rings. Exposure of endothelium-intact rings to L-NAME plus indomethacin also inhibited the hypoxic effect. Our results show that vitamin K(1) prevents the deleterious vascular effects induced by hypoxia, probably due to its action on endothelial cells.
Tirapelli
Carlos R
CR
Department of Pharmacology, Faculty of Medicine, University of São Paulo, Brazil.
Mingatto
Fábio E
FE
de Oliveira
Ana M
AM
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D010837:Vitamin K 1 / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D010837:Vitamin K 1; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin