Intravenous infusions of quantities of aldosterone too small to affect renal function raised the concentration of potassium in the plasma of cats under chloralose anaesthesia (Davey & Lockett, unpublished). This observation indicated extra-renal action of the hormone and raised the question whether the effects of aldosterone on renal function were predoininantly the result of the direct action of this compound within the kidney itself or were, in large part, the consequence of its extra-renal effects. The existence of extra-renal actions of mineralocorticoids is well known; they have been described by Wilson (1957) and Flanagan, Davis & Overmann (1950) amongst others. There has, however, been no direct demonstration of the intrarenal effects of aldosterone under conditions which exclude the possibility of extra-renal effects. The nearest approach to such conditions is found in the work of Barger, Berlin & Tulenka (1958) and of Ganong, Mulrow & Hollinger (1957). Barger and his collaborators studied the effect of infusions of aldosterone into the left renal artery of the dog. Unilateral effects were observed in some of their experiments, but these were preceded by a long latent period, and no observations were made of the effect of their infusions on the concentrations of electrolytes in plasma. Ganong and his colleagues used larger doses of aldosterone and were unable to show that the kidney which received the intra-arterial injection of hormone responded either more markedly or more rapidly than did the other.The object of our experiments was therefore to study the renal actions of aldosterone in kidneys perfused with blood and isolated from all nervous and hormonal continuity with the animal body. METHODSThe cats used were of male, female or neuter sex and weighed from 1-3 to 4-6 kg. Young animals were commonly selected to provide the heart-lung-kidney preparations and the older aniimals were used as blood donors. Only lactating females or those in advanced stage

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A study has been made of the transmitter released in a cat heart-lung preparation when the sympathetic chains were stimulated. The nervi accelerantes were always sectioned before stimulation. The transmitter appeared first in the pulmonary venous blood. In its actions on the heart-lung preparation, it resembled isoprenaline and not adrenaline. Chromatographic studies using three different solvents showed that 80 to 100% of this transmitter consisted of a catechol amine which had R, values which were identical with those of isoprenaline. Pharmacological studies failed to distinguish between the actions of this amine and those of isoprenaline, but clearly differentiated between those of the pulmonary amine, adrenaline, and noradrenaline.The discovery of trace amounts of a third sympathomimetic amine in saline extracts of the adrenal -lands of cats, monkeys, and man has been reported by Lockett (1954). This amine could not be differentiated from isoprenaline (N-isopropylnoradrenaline) by its colour reactions, by its chromatographic behaviour, or by its pharmacological activity; it could, however, readily be distinguished from adrenaline and from noradrenaline both in R, values and by pharmacological means.The possible physiological significance of this trace amine required study. The chemical transmitter of the postganglionic sympathetic nerve fibres supplying bronchi was examined because isoprenaline (Konzett, 1940a) and the third amine of the adrenal gland (Lockett, 1954) had proved more active than adrenaline as dilators of previously constricted bronchioles. Cats were selected for this investigation because the third amine of the adrenals was known to occur in this species (Lockett, 1954). METHODSThe experiments recorded involved 123 cats.Anaesthesia was induced with chloroform and ether (1:4 parts v/v) and was maintained with chloralose, 8 ml./kg. of a 1% w/v solution in 0.9% w/v NaCl in water, given by femoral venous cannula. The anticoagulant used was heparin (Liquemin, Roche), 500 units/kg. body weight. Donor blood, containing very little adrenaline and noradrenaline, was obtained as follows: anaesthetized cats were made spinal, the adrenals were excluded from the circulation, and the sympathetic chains were removed from just above the stellate ganglia to the brim of the pelvis. After an interval of 20 min. the cats were bled from a carotid arterial cannula.Heart-lung preparations were made in adrenalectomized spinal cats by a technique essentiallyifiiiiar tdtimartused by Knowlton and Starling (1912). Systemic outflow was recorded from a simple syphon placed between the peripheral resistance and the reservoirs. The circuit was arranged to allow the return of blood from the syphon recorded to either of two reservoirs. These reservoirs were small double surface condensers, each of 60 ml. maximum capacity. Blood from either reservoir was returned to the heart through a 4 in. Liebig condenser which adjoined the cannula in the superior vena cava. The reservoirs and the Liebig condenser were warmed with water whi...

A sympathomimetic amine, not hitherto described as naturally occurring, was unexpectedly encountered in an experiment in which the adrenaline and noradrenaline, in saline extracts of cat adrenal glands, were being separated chromatographically.In this experiment a chromatogram, made from an aliquot of extract corresponding to just less than one-third of a cat gland, was oxidized, by spraying with a solution of potassium ferricyanide, to convert any primary or secondary catechol amines to the corresponding adrenochromes. Adrenaline and noradrenaline then appeared as red and pink spots respectively, and were identified by means of their RF values. There was, however, an additional very pale pink spot (third amine), with an RF value of approximately 0.7, lying ahead of the adrenaline area from which it was separated by a negative horizontal band of paper. Corresponding bands from another, similar, and adjacent chromatogram were therefore eluted and prepared for biological testing. The eluate from the negative zone separating the adrenaline area from that of the third amine was pharmacologically inert, whereas that from the zone of the third amine was highly active. lforeover, the type of activity encountered in the latter zone differed markedly from that obtained from the adrenaline and noradrenaline areas. The third amine, like adrenaline and unlike noradrenaline, strongly antagonized the action of acetylcholine on the rat uterus. However, when doses of adrenaline and of third amine eluates, which had proved equally active on the rat uterus, were injected intravenously into a cat under chloralose, the adrenaline eluate raised the mean arterial pressure and caused contraction of the nictitating membrane as expected, but the eluate of third amine lowered the blood pressure, caused tachycardia, and was without action on the nictitating membrane.The results of a further investigation of this third amine are presented here in three sections. The first section is concerned with the great similarity between the third amine and isoprenaline. The second section deals with the presence or absence of the third amine in the adrenal glands of various species. Finally, the properties and actions of the third amine have been contrasted with those of lactyladrenaline and lactylnoradrenaline, because these two compounds are known sometimes to arise as artifacts in extracts of adrenal glands. Lactyladrenaline was first isolated by Kendall (1932) and was studied, together with lactylnoradrenaline, by Crawford (1951). Work by Serlin and Goldenburg (1953) on the instability of synthetic noradrenaline in acid ethanol indicated that these so-called lactyl derivatives may prove to be ethers. Their hypothesis has not been investigated; the terms lactyladrenaline and lactylnoradrenaline are here used to refer to compounds which are believed identical with those previously encountered in extracts of adrenal glands by Crawford. METHODSCollection of Adrenal Glands.-Adrenal glands were removed from spinal cats or from cats under anaesthesia (e...