The present experiments show that bradykinin and angiotensin are potent releasers of the medullary hormones, probably mainly adrenaline, from the suprarenal glands. Angiotensin is more potent in this respect than any other known substance. These findings were the outcome of a chance observation made when assaying bradykinin by its depressor action on the arterial blood pressure of the cat. On trying to render the assay more sensitive by removing the abdominal viscera and injecting the bradykinin through the central stump of the coeliac artery at its origin from the abdominal aorta above the suprarenals, bradykinin caused a fall, followed after 20-30 sec by a pronounced rise, in arterial blood pressure associated with acceleration of heart rate. The pressor effect and the cardio-acceleration were abolished after removal of the suprarenal glands and were therefore due to release of their medullary hormones. Such an action of bradykinin has been described in rabbits and rats (Lecomte, Troquet & Dresse, 1961), but no quantitative data of the release have been reported. We therefore investigated quantitatively this adrenaline-releasing effect of bradykinin and related kinins. On extending the experiments to angiotensin an extreme sensitivity of the suprarenal medulla to this peptide was revealed. Three other peptides, vasopressin, oxytocin and substance P, did not have this property. Examined under similar conditions they did not cause a detectable release of adrenaline from the suprarenals.
METHODSThe experiments were performed on 2-3 kg cats anaesthetized with intravenous chloralose. To allow cannulation of the right femoral vein, anaesthesia was induced with ethyl chloride and ether.In order to inject the peptides into the abdominal aorta above the suprarenal glands the cats were eviscerated by removal of the large and small intestine, stomach and spleen, and a metal cannula was tied into the central stump of the coeliac artery. The cannula was a 20-gauge hypodermic needle (No. 0); its sharp end was cut off and a groove made near the
IN a note published some time ago [Dale and Feldberg, 1934] [1932] and Plattner [1932, 1933] found that the substance present in such extracts was rapidly inactivated by fresh blood, like acetylcholine, and that the quantity present had a general correspondence to the wide differences in sensitiveness of different muscles to the stimulating action of acetylcholine. Faradic stimulation of the nerve increased the yield; but P1 attn e r associated the apparent presence of the acetylcholine in the muscle, and its increase on mixed nerve stimulation, with a "parasympathetic" innervation of the blood vessels. In the tongue, excised from a cat treated with eserine, and divided longitudinally into halves, he found that stimulation of the chorda-lingual nerve caused increase of acetylcholine in the extract from one half, while stimulation of the hypoglossal nerve did not significantly increase the yield of the other.Hess [1923], Brinkman and Ruiter [1924, 1925]
The present experiments deal with a new central action of adrenaline, noradrenaline and 5-hydroxytryptamine (5-HT). They show that these amines affect body temperature when injected into the cerebral ventricles of an unanaesthetized cat. 5-Hydroxytryptamine raises the body temperature, whereas adrenaline and noradrenaline have the opposite effect and lower it, partiwlarly when it is elevated by either 5-HT or pyrogens similarly applied. These findings suggest that the three amines which are present in relatively high concentrations in the hypothalamus (Vogt, 1954;Amin, Crawford & Gaddum, 1954) play a role in the hypothalamic regulation of body temperature.The experiments are the outcome of two independent observations, the first of which is concerned with pyrogens and the second with the amines 5-HT, adrenaline, and noradrenaline. Pyrogens injected into the cerebral ventricles of a cat cause long-lasting fever and shivering. When the amines are similarly injected 5-HT produces shivering, whereas adrenaline and noradrenaline abolish drug-induced shivering.Petersdorf & Bennett (1959) produced fever by the injection of pyrogens into the cisterna magna of rabbits. Fever produced in cats by the injection of pyrogens into the cerebral ventricles through an indwelling cannula has been described by Sheth & Borison (1960) as well as by Villablanca & Myers (1963), who in addition noted that shivering occurred. The effects, which were obtained with doses of pyrogen too small to be effective on intravenous injection, occurred after a latency of about 1 hr, and the body temperature remained elevated for many hours.
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