Effects of ouabain on carotid body chemoreceptor activity in the cat.

Abstract

SUMMARY1. The effects of infusions of ouabain on chemoreceptor activity recorded from the peripheral end of a sectioned carotid sinus nerve were studied in cats anaesthetized with pentobarbitone.2. Ouabain caused a marked increase in chemoreceptor discharge followed by a decline in discharge to frequencies near or below the pre-ouabain level; during the latter period further administration of ouabain had no effect.3. Infusion of ouabain during hypoxia further increased the chemoreceptor discharge, but this effect was short-lasting.4. On intracarotid administration ouabain was less effective in cats with the ganglioglomerular (sympathetic) nerves cut, whereas on intravenous administration no significant difference was observed. Following intravenous administration of ouabain the chemoreceptor peak discharge occurred with dose levels similar to those needed to cause cardiac arrhythmias, but following intracarotid administration the chemoreceptor discharge peaked at doses about 40 % of those causing arrhythmias.5. During ouabain-induced excitation the stimulatory action of NaCN, CO2-equilibrated Locke solution and acetylcholine was potentiated, as was the chemoinhibition induced by dopamine. During the post-excitatory period the responses evoked by these substances were reduced or abolished.6. Neither mecamylamine, a nicotinic antagonist, nor physostigmine, an anticholinesterase, affected the response of the carotid chemoreceptors to ouabain.7. The major finding of this study was that ouabain initially 'sensitizes' the carotid body chemoreceptors and then 'desensitizes' them. The most likely mechanism responsible for these effects is the well established Na+-K+-ATPase-inhibiting property of ouabain.

Digoxin increases peripheral chemosensitivity and the ventilatory response to exercise in normal subjects

“…Digoxin increased peripheral chemosensitivity by approximately 50%. This is consistent with previous studies in both animals 17,18 and humans 19 . However, in contrast with results from animals studies, sensitization of the CB did not affect ventilation under normoxic conditions in the present study.…”

“…Digoxin has been part of the therapeutic armamentarium of heart failure for a long time and is currently still recommended for symptomatic patients already receiving optimized standard therapy 16 . Digitalis sensitizes the CB in animals 17,18 and in healthy humans by increasing the ventilatory response to hypoxia, 19 but does not affect sympathetic outflow 19 . Whether this affects exercise tolerance is not known.…”

The Effect of Carotid Chemoreceptor Inhibition on Exercise Tolerance in Chronic Heart Failure

“…Further, patients in these previous studies were not treated with β-blockers or ARBs but were receiving digoxin. Digoxin is no longer the preferred treatment for patients with CHF (Lewis et al, 1989), and has been shown to sensitize the CC (Quest and Gillis, 1971;McQueen and Ribeiro, 1983;Schobel et al, 1994;Janssen et al, 2010). Future clinical trials investigating the effect of CC-mediated CV function before and after treatment may provide further insight into the benefits of pharmacotherapy on CC function.…”

Regulation of cough by neuronal Na+–K+ ATPases

“…At sensory nerve terminals, a sodium pump Sodium pump regulation of cough Canning and Farmer 141 [52,53]. Inhibition of sodium pump function may acutely increase generator potential amplitude and thus terminal excitability [54][55][56]. But with sustained and/or marked inhibition, an accumulation of Na + at the terminals would eventually develop and would impair gating of Na + channels involved in both generator potential formation but also action potentials.…”