Delay by bretylium of adrenergic nerve degeneration after sympathectomy of the submaxillary gland.
Administration of 24 mumol/kg of bretylium 10 h after ganglionectomy delayed the loss of endogenous norepinephrine and the impairment of neuronal uptake of 3H-metaraminol (3H-MA) that follow sympathetic denervation. This delay was evident 16 and 20 h after denervation. Twenty four h after ganglionectomy, when NE stores and uptake of 3H-MA were reduced to their lowest values in untreated rats, in bretylium-treated ones these values were approximately 40% of those in normal glands. The onset of degeneration secretion in treated rats was delayed by about 9 h. The development of prejunctional supersensitivity was also delayed. The subcellular distribution of NE in normal and 16 h denervated glands showed that denervation reduced the neurotransmitter to the same extent in the 3 fractions: coarse, supernatant and microsomal. Treatment with bretylium and pargyline prevented the loss of NE from the microsomal fraction. Previous administration of pargyline antagonized the protection of 3H-MA uptake seen in 28 h denervated rats treated with bretylium. However, this drug combination induced a greater retention of endogenous NE 24 h after denervation. Bretylium inhibited intraneuronal MAO by 40%. It is concluded that bretylium treatment can delay the degeneration of adrenergic nerve terminals separated from the cell bodies by a pharmacological effect probably not related to MAO inhibition or to its neurone blocking action.
D000818:Animals; D001949:Bretylium Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008680:Metaraminol / Q000378:metabolism; D008995:Monoamine Oxidase / Q000032:analysis; D009410:Nerve Degeneration / Q000187:drug effects*; D009411:Nerve Endings / Q000187:drug effects; D009638:Norepinephrine / Q000032:analysis; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D012463:Saliva / Q000378:metabolism; D013363:Submandibular Gland / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013997:Time Factors
D001949:Bretylium Compounds; D008680:Metaraminol; D010293:Pargyline; D008995:Monoamine Oxidase; D009638:Norepinephrine