Effects of sinoaortic denervation on the reflex actions of digoxin and a polar aminocardenolide.
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 approximately 100 min (0.7 and 1.2 micrograms/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 micrograms/kg i.v. in 10 min) caused a progressive increase in cardiac VANA in a 60-min observation period. Neither digoxin, at less than or equal to 120 micrograms/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.
Rebagay
W R
WR
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912.
Caldwell
R W
RW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002301:Cardiac Glycosides / Q000494:pharmacology*; D003714:Denervation; D004073:Digitoxigenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D012849:Sinoatrial Node / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology
D002301:Cardiac Glycosides; D004073:Digitoxigenin; D004280:Dobutamine; C012114:ASI-222; D010042:Ouabain; D004077:Digoxin