Inhibitory effect of GABA on cerebrovascular sympathetic neurotransmission

The possibility that gamma-aminobutyric acid (GABA) could modulate sympathetic neurotransmission in the cerebrovascular bed of the goat has been investigated by means of 3 experimental approaches: measurement of cerebral blood flow in the anesthetized animal, recording of isometric tension in isolated cerebral arteries, and measurement of tritium efflux from cerebral arteries preloaded with [3H]noradrenaline. Electrical stimulation of cervical sympathetic nerve produced reductions in cerebral blood flow which were significantly diminished during continuous infusion of GABA (20-40 micrograms/min) into the internal maxillary artery. Picrotoxin (3 mg) did not change the inhibitory effect of GABA. Exogenously administered noradrenaline (1-9 micrograms) and tyramine (50-500 micrograms) reduced cerebral blood flow as well, but this effect was unchanged by GABA infusion. Transmural electrical stimulation elicited frequency-dependent contractile responses in isolated cerebral arteries which were significantly blocked when GABA was present, at a dose (10(-4) M) which did not modify the contractile response to exogenous noradrenaline (10(-8)-10(-4) M). Moreover, GABA (10(-5)-10(-4) M) inhibited transmural electrical stimulation-evoked tritium efflux from arteries preloaded with [3H]noradrenaline. These results show that GABA inhibits adrenergic neurotransmission in cerebral arteries by a mechanism involving inhibition of transmitter release. Probably, specific presynaptic GABA-B receptors mediate this inhibitory effect.