Selective noradrenergic denervation of the heart following intravenous injections of vinblastine or vincristine.
1. The progressive effects of a single injection (3mg/kg i.v.) of either vinblastine or vincristine on the innervation of the rat atria have been examined. 2. Functional studies were performed by stimulating electrically the noradrenergic or cholinergic nerve fibres within isolated left atria from treated and control rats. In addition, the effects of the drugs on the ultrastructure of both types of nerve fibre were examined. The noradrenergic innervation was further examined by fluorescence histochemistry and measurement of the noradrenaline content of the atria. 3. On the basis of these studies it appeared that both drugs caused degeneration of noradrenergic nerves; cholinergic nerves seemed to be unaffected. Marked effects were seen 48 h after vinblastine treatment or 30 h after vincristine treatment. 4. Evidence is presented and discussed as to whether or not this action of the vinca alkaloids can be ascribed to their well-established effects on microtubules and intra-axonal transport processes.
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D003714:Denervation; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D006325:Heart Atria / Q000648:ultrastructure; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009410:Nerve Degeneration; D009638:Norepinephrine / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000502:physiology; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014747:Vinblastine / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology*
D014750:Vincristine; D014747:Vinblastine; D009638:Norepinephrine