POSSIBLE MECHANISMS FOR THE PROTECTIVE ACT OF ALPHA-TOCOPHEROL VASCULAR HYPOXIA

1 The mechanism of the protective action of alpha-tocopherol (vitamin E) in sustaining noradrenaline-induced responses in vascular hypoxia w as investigated using pharmacological methods. 2 Four vascular spasmog enic agents, methoxamine, acetylcholine, histamine and potassium, each with a different mode of action were used to produce responses in gui nea-pig isolated portal vein. In each case the responses were signific antly reduced by hypoxia or hypoxia and a substrate-free environment. 3 Pre-incubation of the vein with alpha-tocopherol protected the norad renaline-induced responses against hypoxia in the substrate-free envir onment. However, at the EC(50) concentration for protection of noradre naline, alpha-tocopherol failed to protect the responses of each agent from the inhibitory effects of hypoxia, suggesting a mechanism of pro tection involving noradrenaline. 4 Drugs known to interfere with the d isposition of noradrenaline in sympathetically innervated tissues, coc aine, hydrocortisone and tyramine did not affect the response to alpha -tocopherol. 5 Responses to calcium were unaffected by alpha-tocophero l in normoxia and hypoxia. 6 The protective action of alpha-tocopherol was not mimicked by the chromanol ring of the vitamin structure, Trol ox C, suggesting that the vascular protection in hypoxia was not depen dent on an antioxidant mechanism. 7 However, the glycolytic enzyme inh ibitor, iodoacetic acid, prevented the protective action of the vitami n in hypoxia, suggesting that alpha-tocopherol enhanced noradrenaline- mediated activity in hypoxia through an iodoacetic acid-sensitive path way.