Pharmacological characterization of GABA receptors mediating vasodilation of verebral arteries in vitro.

GABA (gamma-aminobutyric acid) produced a dose-dependent dilation of isolated cat and dog cerebral artery segments which had been given an active, tonic contraction by either prostaglandin F2 alpha or serotonin. No effect of GABA on extracranial blood vessels was observed. The GABA-induced dilation could be blocked in a dose-dependent manner by either bicuculline or picrotoxin. The latter agent appeared to act as a competitive antagonist. GABA agonists muscimol, imidazoleacetic acid, delta-aminovaleric acid, (+/-)gamma-amino-beta-hydroxybutyric acid, and beta-alanine also relaxed actively contracted cerebral arteries dose-dependently. The relative potency of these agonists was consistent with that established for GABA receptors on neurons and invertebrate striated muscle. GABA was also tested on two human cerebral arteries and found to cause a small dilation. The results support the existence of a cerebrovascular GABA receptor which may mediate an interaction between GABA and the cerebral circulatory system.