Effect of transient vagal cold blockade upon reflex actions of a polar and nonpolar cardiac glycoside

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Abstract

To determine the role of vagal afferent fibers in expressing the actions of a polar aminosugar digitalis agent [ASI-222 (4-amino-galactose β-D- digitoxigenin HCl)] and a nonpolar neutral sugar agent (digoxin) on cardiac sympathetic nerve activity (CSNA), we utilized a period of vagal cooling to block traffic in that nerve. Anesthetized dogs were prepared to measure CSNA in efferent fibers from the right stellate ganglion. Both vagi were exposed midcervically and fitted with water-filled glass coils. The vagi were cooled (~4°C) and then either ASI-222 or digoxin was infused i.v. at dose rates which produce cardiac arrhythmias after about 100 min. Saline was infused in a third group. After 50 min of drug infusion, the vagi were rewarmed. During vagal cooling and infusion of saline or ASI-222, CSNA rose by 25 to 30%. Within 10 min after rewarming, CSNA returned to baseline values in the saline group but nerve activity in the ASI-222 group promptly fell about 45% below base line and remained depressed. This dose rate of ASI-222 depresses CSNA in neurally intact dogs within 30 min. In contrast, during vagal cooling digoxin caused a slow but progressive fall in CSNA (~20%); with rewarming and higher doses, CSNA began to rise above baseline levels. This profile of changes in CSNA to digoxin is similar to that observed in neurally intact animals. In other dogs given atropine to block the effects of efferent vagal nerve traffic, ASI-222 produced a prompt decline in CSNA like that observed previously in neurally intact dogs. In conclusion, the polar ASI-222 appears to reduce CSNA via vagal afferent nerves. Digoxin can reduce CSNA in the absence of vagal nerve function, possibly via interaction with other reflex receptor areas, e.g., carotid sinus baroreceptors.

Original languageEnglish (US)
Pages (from-to)1022-1027
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume262
Issue number3
StatePublished - Jan 1 1992

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Cardiac Glycosides
Reflex
Digoxin
Dogs
Rewarming
Stellate Ganglion
Carotid Sinus
Pressoreceptors
Digitalis
ASI-222
Atropine
Glass
Cardiac Arrhythmias
Water
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of transient vagal cold blockade upon reflex actions of a polar and nonpolar cardiac glycoside. / Caldwell, Robert William; Rebagay, W. R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 262, No. 3, 01.01.1992, p. 1022-1027.

Research output: Contribution to journalArticle

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