Facilitation of noradrenaline release from sympathetic nerves through activation of ACTH receptors, β‐adrenoceptors and angiotensin II receptors

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Abstract
1 In rabbit pulmonary artery and left atrial strips previously incubated with [3H]-noradrenaline, the active fragment of adrenocorticotropic hormone (ACTH1–24, 0.1 μm) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity when a cocktail containing corticosterone (40 μm), cocaine (30 μm) and propranolol (4 μm) was present, but not in the absence of these drugs. In rabbit pulmonary artery a facilitatory effect of ACTH1–24 (0.1μm) was also observed when only cocaine (30 μm) was present. 2 ACTH1–24 (0.1 μm) did not affect the S-I outflow of radioactivity from rat atria, rat pulmonary artery or guinea-pig pulmonary artery, either in the presence or in the absence of the cocktail containing corticosterone (40 μm), cocaine (30 μm) and propranolol (4 μm). These results suggest that the presence of facilitatory prejunctional ACTH receptors may be restricted to rabbit sympathetic nerve endings. 3 Angiotensin II (0.01 μm), but not isoprenaline (0.1 μm) or ACTH1–24 (0.1μm), significantly enhanced the S-I outflow of radioactivity from rabbit pulmonary artery. In the presence of phentolamine (1 μm) to block inhibitory α2-adrenoceptors, the facilitatory effect of angiotensin II (0.01 μm) was significantly enhanced, and a significant facilitatory effect of isoprenaline (0.1 μm) and of ACTH1–24 (0.1 μm) was then revealed. These results suggest that feedback inhibition of noradrenaline release, mediated through the prejunctional α2-adrenoceptor mechanism, buffers increases in noradrenaline release during activation of facilitatory prejunctional receptors. 4 In rabbit pulmonary artery, two concentrations of 8-Br-cyclic AMP, (270 or 540 μm), enhanced the S-I outflow of radioactivity in the presence of phentolamine (1 μm) to a similar extent. In the presence of 8-Br-cyclic AMP (270 μm) and phentolamine, the facilitatory effects of isoprenaline (0.1 μm) and of ACTH1–24 (0.1 μm) were blocked, whereas that of angiotensin II (0.01 μm) was not changed. These results suggest that both prejunctional β-adrenoceptors and ACTH receptors enhance noradrenaline release by generating cyclic AMP. The mechanism by which angiotensin II facilitates noradrenaline release is probably independent of the cyclic AMP second messenger pathway.

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