Pharmacological studies of ganglionic transmission: Antagonism by histamine and imidazole-4-acetic acid against the stimulant effect of angiotensin II on cardiac sympathetic agnglia in dogs

Abstract

Histamine (HA), imidazole-4-acetic acid (IAA) and angiotensin II (AT II) were administered to the cardiac sympathetic ganglia through the right subclavian artery (i.a.) in spinal dogs. IAA, a metabolite of HA, at a dose of 500 ug, induced a marked inhibition of the rate increase produced by 1 and 2 μg AT II, 10 and 20 μg bethanechol (BCH), and 5 and 10 μg dimethylphenylpiperazinium (DMPP). This inhibition was strongly antagonized by i.a. injection of Picrotoxin, 5 mg, and partly inhibited by the’ same dose of bicuculline. Single i.a. injection of HA did not inhibit the positive chronotropism induced by these three ganglionic stimulants, but three repeated i.a. injections of 50 or 100 ug HA, at the interval of 5 min rendered the ganglion insensitive to the same dose of HA and also inhibited the positive chronotropism produced by AT II and BCH, but not by DMPP. The inhibition by the repeated HA administration of the AT II and BCH-induced rate increase was not antagonized by i.a. injection of Picrotoxin or i.v. injection of 10 mg/kg aminoguanidi ne, an inhibitor of histaminase and monoamine oxidase. The results suggest that IAA counteracts ganglionic stimulant effects of AT II, BCH and DMPP by acting on γ-aminobutyric acid (GABA) receptors located at the ganglia as similarly does GABA, whereas the repeated administration of HA inhibits the ganglionic stimulant effects of AT II and BCH through mechanisms other than the GABA-ergic one which is mediated via endogenous IAA formed by exogenous HA.