Mechanism of histamine-induced epinephrine release in guinea pig

The aims of this study were to provide direct evidence that in anesthetized guinea pigs i.v. administration of histamine induces sympathoadrenal activation and to identify the source and mechanism of histamine-induced epinephrine release. Plasma epinephrine measurements were used as the index of sympathoadrenal activity. In intact guinea pigs, histamine infusion caused a 3-fold rise in plasma epinephrine levels. In guinea pigs pretreated with 6-hydroxydopamine to obtain chemical sympathectomy, the rise in plasma epinephrine induced by histamine was distinctly smaller than in controls. This rise was completely inhibited in guinea pigs pretreated with the ganglion blocking agent hexamethonium and in pithed guinea pigs. Pretreatment with the H2-receptor antagonist cimetidine or the H1-receptor antagonist mepyramine reduced the rise in plasma epinephrine. These results demonstrate that in guinea pigs, epinephrine is released not only from the adrenal medulla but also from nerve endings and that histamine releases epinephrine by indirect action through central reflex pathways.