脳-心連関と附子成分による制御 Peripherally administered compounds derived from processed aconite extract cause bradycardia through hypothalamic-pituitary-adrenal axis in mice
We investigate the mechanisms of interaction between aconitine and higenamine (component compounds contained in processed aconite extract) for pulse rate and for chronotropy in isolated right atria of, mice. (1) Higenamine (peripherally β 1-adrenergic) enhanced aconitine-incuced tachyarrhythmia, and aconitine enhanced higenamineinduced positive inotropy in isolated right atria. (2) Aconitine (i.p. and i.c.v. injected) induced bradycardia in mice. (3) Aconitine (i.p.)-induced bradycardia was inhibited by scopolamine (s.c.), and atropine (i.c.v.), but not by hexamethonium (i.c.v.)and mecamylamine (i.c.v.). Aconitine (i.c.v.) induced bradycardia was inhibited by sooplamne and atropine (i.c.v.). (4) Aconitine (i.p.)-induced bradycardia was hardly generated in mice by the bilateral lesions of anterior hypothalamic area and by bilateral adrenalectomy. (5) In two groups of diabeticKK-CA<SUP>m</SUP> mice specifically bred for high and low sensitivity to acetylcholine (ACh), aconitine (i.p.) caused bradycardia, which was counteracted by higenamine (i.p.) in ACh-low sensitive but not in ACh-high sensitive mice. These results demonstrate that peripherally admnstered aconitine induces bradycardia by muscarinic mechanisms through hypothalamio-pituitary adrenal axis, which is counteracted by peripherally β1 -adrenergic higenamine.
日本薬理学雑誌 106, 87-91, 1995-09-01