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.
Miranda
F J
FJ
Research Center, Hospital La Fe, Valencia, Spain.
Torregrosa
G
G
Salom
J B
JB
Campos
V
V
Alabadí
J A
JA
Alborch
E
E
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002536:Cerebral Arteries / Q000294:innervation* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004558:Electric Stimulation; D005260:Female; D006041:Goats / Q000502:physiology*; D007537:Isometric Contraction / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D009638:Norepinephrine / Q000493:pharmacokinetics; D010852:Picrotoxin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001418:Baclofen; D009638:Norepinephrine; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid