Sensory fibres modulate histamine-induced catecholamine secretion from the rat adrenal medulla and sympathetic nerves.

1. We have studied the mechanism of catecholamine secretion induced by histamine from the adrenal medulla and sympathetic noradrenergic neurones in the rat, and the role of capsaicin-sensitive sensory nerves in this secretion. 2. Histamine at a dose of 1 mg/kg induced adrenaline and noradrenaline secretion by a non-neurogenic mechanism. In contrast, at a dose of 3 mg/kg it induced adrenaline and noradrenaline secretion by both non-neurogenic and neurogenic mechanisms. 3. The adrenaline released in response to histamine at 3 mg/kg was exclusively of adrenal origin whereas the noradrenaline released was of non-adrenal origin (most probably noradrenergic sympathetic nerves). As with its action on the adrenal, histamine induced noradrenaline secretion from these extra-adrenal tissues by both neurogenic and non-neurogenic mechanisms. 4. When adrenaline secretion from the adrenal gland was impaired by adrenal denervation and/or adrenalectomy, the plasma noradrenaline secretion was increased. This is most probably due to compensation from the rest of the sympathetic nervous system. This compensatory increase in noradrenaline was abolished by hexamethonium, which indicates that it was mediated by a cholinergic mechanism. 5. Pre-treatment of rats as neonates subcutaneously with capsaicin (a selective neurotoxin for certain sensory nerves) at a dose of 50 mg/kg, had no effect on the non-neurogenic secretion of catecholamine induced by histamine. In contrast, capsaicin pre-treatment abolished the neurogenic catecholamine secretion in response to histamine as well as the neurogenic compensatory increase in plasma noradrenaline levels that occurred when adrenaline secretion by the adrenal gland was impaired. 6. In the present study, by using histamine as a form of stress, we have been able to provide evidence not only (a) to confirm a role for capsaicin-sensitive sensory fibres in modulating neurogenic adrenaline secretion from the adrenal gland, but also (b) to suggest a similar role for these fibres in modulating neurogenic noradrenaline release from sympathetic noradrenergic nerves in response to histamine and in response to impairment of adrenaline secretion by the adrenal gland.