Inhibition of receptor-mediated noradrenaline release from the sympathetic nerves of the isolated rabbit heart by anaesthetics and alcohols in proportion to their hydrophobic property.

The actions of anaesthetics (diethyl ether, enflurane, chloroform, methoxyflurane) and alcohols (ethanol, 1-propanol, 1-butanol, 1-pentanol) on the noradrenaline release from (and uptake into) the sympathetic nerve terminals were studied in isolated rabbit hearts perfused with Tyrode solution at constant flow rate. The noradrenaline in the perfusate was assayed spectrofluorimetrically. 1. Ethaonol, 1-propanol, 1-butanol and all anaesthetics (at concentrations which decreased by more than 65% the noradrenaline output in response to activation of the nicotinic receptors) did not significantly affect the spontaneous noradrenaline output. Only 1-pentanol (3.75 X 10(-3) M) caused an increase in spontaneous noradrenaline output. 2. The uptake of exogenous noradrenaline from the perfusion fluid into the sympathetic nerve terminals was not influenced by the anaesthetics and alcohols (at concentrations which decreased by more than 65% the noradrenaline output evoked by stimulation of the nicotinic receptors). 3. All anaesthetics and alcohols caused a concentration-dependent inhibition of the noradrenaline release in response to activation of the nicotinic receptors on the nerve terminals by 1,1-dimethyl-4-phenylpiperazine or acetylcholine in the presence of atropine. The concentrations of the compounds which decreased the noradrenaline output by 50% were as follows: diethyl ether: 5.1 X 10(-3) M; enflurane: 2.9 X 10(-4) M; chloroform: 2.6 X 10(-4) M; methoxyflurane: 3.8 X 10(-5) M; ethanol: 1.5 X 10(-1) M; 1-propanol: 1.9 X 10(-2) M; 1-butanol: 6.0 X 10(-3) M; 1-pentanol: 1.2 X 10(-3) M.