vitamin-k-1 and Hypoxia

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.

Topics: Animals; Carotid Arteries; Dose-Response Relationship, Drug; Endothelium, Vascular; Hypoxia; In Vitro Techniques; Indomethacin; Male; Muscle Contraction; Muscle, Smooth, Vascular; NG-Nitroarginine Methyl Ester; Nitric Oxide; Phenylephrine; Rats; Rats, Wistar; Vasoconstrictor Agents; Vitamin K 1

In hypoxia, but not normoxia, alpha-tocopherol (vitamin E) acts as an agonist in guinea-pig isolated colon, producing dose-dependent increases in contractile activity. This effect is mimicked by agents, vitamin K1 and phytol, which contain a structural similarity to the phytol side chain of alpha-tocopherol, but is antagonized by vitamin K3 which has a structure similar to the chromane ring of vitamin E. All of the agonist responses were blocked by atropine and potentiated by physostigmine but were unaffected by hexamethonium. However, responses to acetylcholine were not antagonized by vitamin K3 and these data suggest that alpha-tocopherol, phytol, vitamins K1 and K3 may be acting on a 'hypoxia receptor' which mediates release of acetylcholine onto muscarinic receptors.

Topics: Acetylcholine; Animals; Colon; Gastrointestinal Motility; Guinea Pigs; Hypoxia; In Vitro Techniques; Phytol; Receptors, Muscarinic; Vitamin E; Vitamin K; Vitamin K 1