CHARACTERISTICS OF THE PROTECTIVE ACTION OF ALPHA-TOCOPHEROL IN VASCULAR HYPOXIA

The functioning of the guinea-pig isolated portal vein was monitored b y measuring spontaneous mechanical activity responses to electrical st imulation and administered noradrenaline in normoxic conditions. The e ffect of hypoxia, induced by bubbling the physiological bathing soluti on with a 95% N-2/5% CO2 gas mixture, on the mechanical performance of the vein was then assessed. Spontaneous activity declined in hypoxia, with mean contraction tension reduced by 55+/-8.8%. The responses to electrical field stimulation (2-32 Hz, 0.7 msec. 70 V) were lowered by 14+/-4.6% but contractions produced by a range of noradrenaline conce ntrations (0.01-160 mu M) were unaffected by hypoxia. Substitution of glucose in the bathing solution with sucrose, a substrate unavailable to the cells for energy generation, produced a marked enhancement of t he effect of hypoxia. Spontaneous activity was reduced by 76+/-8.3%, e lectrically-induced activity by 80+/-14.4% and noradrenaline-induced r esponses by 85+/-6.8%. Although in normoxia the activity and responses of the portal vein were unaffected by the presence of alpha-tocophero l, it significantly protected the functioning of the vein in hypoxic c onditions. This effect was concentration-dependent within the range 10 -160 mu M and was most marked when glucose was replaced by sucrose in the bathing solution.