Effects of sinoaortic denervation on the reflex actions of digoxin and a polar aminocardenolide

Winona R. Rebagay, Robert W. Caldwell

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

To determine the role of carotid sinus and aortic arch baroreceptors in the reflex cardiac sympathetic nerve activity (SNA) responses to administration of ASI-222, a polar aminocardenolide, and to digoxin, a neutral cardenolide, we used anesthetized dogs from which these reflex receptor areas had been removed. The SNA was measured in postganglionic fibers from the stellate ganglion. After we made baseline measurements, we infused either ASI-222 or digoxin intravenously (i.v.) at dose rates that produce cardiac arrhythmias in -100 min (0.7 and 1.2 μg/kg/min), respectively. Our data indicate that with sinoaortic baroreceptors removed, progressive infusion of digoxin increases cardiac SNA. In contrast, cardiac SNA decreases progressively during continuous infusion of ASI-222. In saline-treated dogs, SNA was not significantly altered. In another series of experiments, we examined the effects of these drugs and saline on cardiac vagal afferent nerve activity (VANA). ASI-222 (50 μg/kg i.v. in 10 min) caused a progressive increase in cardiac VANA in a 60-min observation period. Neither digoxin, at 120 μg/kg i.v. in 100 min, nor saline altered VANA. Digoxin appears to reduce SNA by interacting with the carotid sinus and aortic arch baroreceptors, which are myelinated. It does not affect VANA acutely. In contrast, ASI-222 appears to decrease cardiac SNA by interacting with other reflex receptor areas-the unmyelinated cardiopulmonary afferent nerve endings, particularly cardiac mechanoreceptors.

Original languageEnglish (US)
Pages (from-to)45-51
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume19
Issue number1
DOIs
StatePublished - Jan 1992

Keywords

  • Aminocardenolide
  • Autonomic reflexes
  • Digoxin
  • Sinoaortic denervation

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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