The action of peptides on the adrenal medulla. Release of adrenaline by bradykinin and angiotensin

Abstract

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

Role of noradrenaline in the acute pressor response to angiotensin in conscious cats

“…Thus, the pressor potency was reduced by treatment with the catecholamine depleting substances, reserpine and syrosingopine, and was restored by infusions of catecholamines. Similarly, inhibition of monoamine oxidase which has been shown to increase peripheral levels of catecholamines (Goldberg & Shideman, 1962;Sanan & Vogt, 1962) (Feldberg & Lewis, 1964, 1965Vane, 1969 (Bickerton & Buckley, 1961) and via central vagal inhibition (Scroop & Lowe, 1968). The failure of both pempidine and bethanidine to reduce the angiotensin pressor responses in the present experiments argues against a significant central component to the response.…”

The Circulatory Effects of Bradykinin in Normal Subjects and Patients With Chronic Bronchitis

“…The possibility still remains however that the phenomenon represents true tachyphylaxis, the organs responding less to the same concentration of the active agent. Feldberg & Lewis (1964) showed that bradykinin releases catechol amines from the adrenal medullae in the anaesthetized cat. If this occurs also in man, it is possible that the level of circulating catechol amines may have risen as the infusion of bradykinin continued in the present experiments and that this may have led to the observed secondary increase in systemic blood pressure.…”

The balloon catheter induces an increase in contralateral carotid artery reactivity to angiotensin II and phenylephrine

“…Ang II facilitates sympathetic transmission, inhibits norepinephrine reuptake (Starke, 1977) and releases catecholamine from the adrenal medulla (Feldberg & Lewis, 1964). Additionally, the renin-angiotensin system modulates the kallikrein-kinin system, a regulatory system involved in a multitude of physiologic and pathologic conditions.…”