EFFECTS OF VINBLASTINE ON NORADRENERGIC AXONS

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Abstract
1 The effects of vinblastine and 6-hydroxydopamine (6-OHDA) on various parameters of adrenergic neurone functions in the rat were examined and compared. 2 During the first 12 h after injection of vinblastine, although the concentration of cardiac noradrenaline was unaltered, the turnover rate of the catecholamine in the heart was reduced to 40 ng g−1 h−1 compared to a rate of 66 ng g−1 h−1 in the hearts of animals treated with 0.9% w/v NaCl solution. 3 The uptake of noradrenaline by rat atria in vitro was inhibited by vinblastine (2.5 × 10−4 m) or 6-OHDA (5 × 10−5 m), but only the inhibitory effect of vinblastine was readily reversible. The in vitro uptake of noradrenaline by atria of vinblastine- or 6-OHDA-treated rats was found to be impaired two days after injection of the drugs. After 14 days, however, the noradrenaline uptake was 71% of control values after vinblastine and 91% after 6-OHDA. 4 In addition to intensely fluorescent nerve trunks in epicardial connective tissue septa, a decrease in the number of fluorescent adrenergic terminals in the atria and ventricles could be observed two days after vinblastine injection. It is suggested that intravenous vinblastine treatment, like 6-OHDA, results in the destruction of adrenergic nerve terminals.