Mode of action of guanethidine on adrenergic neurons and its dependence on sodium

Abstract

Interactions between action of guanethidine (4×10-6 to 4 × 10-5) and Ca, Na or K were investigated in isolated hearts of rabbits. Positive chronotropic responses to electrical sympathetic stimulation and noradrenaline (NA) released by nicotine or high KC1 were measured. Inhibitory drug action on responses was irreversible and reduced by raising Ca to 12.5 mM together with drug addition. The action was not reduced after the drug had been washed out and the Ca level was raised to 50 mM, after which it returned to normal. It was accelerated by lowering Na to 86 mM simultaneously, but not delayed by raising Na to 286 mM. After the drug was washed out with normal solution, NA released by 100 and 300 mM KC1 was reduced to almost the same extent. When stimulation was done during washing with low Na solution, inhibitory drug action on responses and NA released by nicotine was reduced. It was not reduced, however, when nicotine was applied in normal Na solution after washing with low Na solution. During washing with high Na solution, it was accentuated, despite no modification by washing with isoosmotic sucrose or Li solution. Low or high Na solution alone did not modify the parameters. During washing with low K solution (3.5 mM), it was not modified. The hypothesis is presented that guanethidine increases permeability of nerve ending membrane to Na, thereby leading to adrenergic neuron blockade.