Modifications by Propranolol of the Response of Isolated Rabbit Atria to Endogenous and Exogenous Noradrenaline

Lucchesi, Whitsitt & Brown, 1966) and antifibrillatory properties (Benfey & Varma, 1966; Rowlands, Howitt & Markman, 1965) and is effective in relieving symptoms of angina pectoris (Keelan, 1965 ; Gillam & Prichard, 1965).The autonomic innervation of the heart may be involved in cardiac arrhythmias, fibrillation, increase in cardiac work, and coronary vasoconstric- tion, but little is known about the interactions between propranolol and the cardiac autonomic innervation.Benfey & Varma (1964) showed that propranolol competitively inhibits an increase in force and rate of beat of isolated guinea-pig atria produced by noradrenaline but non- competitively inhibits the response to tyramine and butyrylcholine.Desmethylimi- pramine, which inhibits uptake of noradrenaline by storage sites (Iversen, 1965;Titus, Matussek, Spiegel & Brodie, 1966), potentiates the increase in heart rate induced by sympathetic nerve stimulation and prolongs the duration of the response (Toda, Matsuo and Konishi, unpublished).We have investigated the blocking action of propranolol on atrial responses to noradrenaline released by nerve stimulation and by tyramine in comparison with the responses to exogenous noradrenaline. METHODSForty-eight albino rabbits of either sex, weighing 1.8-2.2kg, were used.Under ether anaesthesia the sympathetic nerves, vagi and common carotid arteries were dissected free from surrounding tissues along the cervical trachea.The animals were killed by bleeding from the common carotid arteries, and a block of tissue including sympathetic nerves, vagi, heart, and adherent tissues was isolated postvertebrally as previously described (Toda & West, 1967; Toda & Shimamoto, 1968).The ventricles were discarded.Atria with attached sympathetic nerves were prepared in warmed, oxygenated nutrient solution.In some experiments conventional atrial preparations were used.The composition of the modified Ringer solution was as follows (m-moles/l.):Na, 162.1 ; K, 5.4; Ca, 2.2; Cl, 157.0;HCO3, 14.9; dextrose, 5.6.The isolated atria were attached to a force- displacement transducer (Nihonkoden Kogyo Co.) and suspended in a 60 ml.muscle bath filled with the nutrient solution, gassed with a mixture of 95% oxygen and 5% carbon dioxide and maintained at 300 ±0.50 C. All atria were allowed to equilibrate for 60 to 90 min before the addition of any drug.