Nicotine‐like Actions in Auricles and Blood Vessels After Denervation

Abstract

The work to be described in this paper is a continuation of observations made on the action of nicotine and acetylcholine in the isolated auricles of the rabbit heart and in the perfused vessels of the rabbit ear (Kottegoda, 1953a(Kottegoda, , 1953b. Nicotine and acetylcholine were found to stimulate the auricles in the presence of atropine, and the stimulant action was blocked by hexamethonium. Similarly nicotine was found to constrict the vessels of the rabbit ear; acetylcholine in the presence of atropine or when the perfusion had continued for 24 hours had the same effect. This constrictor action was blocked by hexamethonium; in the presence of benzylimidazoline (Priscol) the constrictor action was reversed to a dilator action, and this dilator action was also blocked by hexamethonium. The observations suggested that the actions of nicotine and of acetylcholine were indirect and were due to the liberation of an adrenaline-like substance. Because of these and various other findings discussed later further experiments were undertaken to test the action of nicotine and acetylcholine on auricles and on vessels which had been denervated some time previously.For experiments on auricles, cats were used in place of rabbits, as the former were found to stand the operation better. A few auricles from normal cats were tested with nicotine and acetylcholine in the presence of atropine; it was found that they behaved like rabbit auricles towards these substances. METHODSCat Auricles. Both stellate ganglia were removed from cats under ether and pentobarbitone sodium (30 mg./kg. body weight intraperitoneally). After 12 to 14 days the animals were killed, the auricles dissected out, and the response to acetylcholine and nicotine tested according to the method described earlier (Kottegoda, 1953a).

Studies on the responses of the isolated nictitating membrane of the cat

“…Similar actions of nicotine have previously been described on the smooth muscle in the vessels of the frog's hind legs (Loewi, 1937), on the smooth muscle in the vessels of the rabbit's ear (Ginzel & Kottegoda, 1953) and in the walls of the bronchi (D. F. Hawkins & W. D. M. Paton, unpublished), structures which are normally assumed to be free from ganglion cells. It seems almost certain that the responses of the isolated nictitating membrane to nicotine and tetramethylammonium are produced indirectly through the release of adrenaline and/or noradrenaline.…”

“…Microscopical sections did, however, show large numbers of fine nerve fibres lying amongst the muscle and it seems most probable that these are the structures stimulated by nicotine and tetramethylammonium and are, in fact, the postganglionic nerve fibres to the muscle. These substances might stimulate either the trunk or the fine endings of these nerves and possibly produce a local axon reflex, as was suggested by Ginzel & Kottegoda (1953) when they investigated the action of nicotine in the vessels of the rabbit's ear. Although Evans & Schild (1953a, b) have demonstrated instances in which nicotine appears to act directly on smooth muscle, it is difficult to believe that this occurs in the normal isolated nictitating membrane.…”

Some Aspects of the Pharmacology of an Homologous Series of Choline Esters of Fatty Acids

“…A stimulating action on the isolated rabbit or cat heart by ganglionic stimulants such as nicotine and ACh after atropine was described by Hoffmann, Hoffmann, Middleton and Talesnik (1945) and more recently on the isolated rabbit auricles by Kottegoda (1953) and Ginzel and Kottegoda (1953). The latter authors found that this effect could be blocked by HMI, and assumed the presence of peripheral sympathetic ganglia within the auricular tissue.…”

The influence of acute sympathetic denervation, reserpine and choline xylyl ether on vagal escape

“…Moreover, the fact that tachycardia can be induced by acetylcholine or by vagal stimulation in the atropinized heart (Jourdan & Nowak, 1936; Kabat, 1939;Brown & Maycock, 1942; Hoffmann, Hoffmann, Middleton & Talesnik, 1945;Heymans & Bennati, 1949) suggests the possibility that acceleration occurs through the activation of sympathetic structures (ganglia and/or chromaffin tissue) located in the myocardium (Heymans & Bennati, 1949;Ginzel & Kottegoda, 1953; Burn, Leach, Rand & Thompson, 1959). Other findings suggesting a possible peripheral activation of adrenergic structures by acetylcholine have been presented by Burn & Rand (1959).…”