Brain Research, 492 (1989) 45-52 45 Elsevier BRE 14620 Inhibitory effect of GABA on cerebrovascular sympathetic neurotransmission Francisco J. Miranda, Germ~in Torregrosa, Juan B. Salom, Vicente Campos, Jos6 A. Alabadi and Enrique Alborch Research Center, Hospital 'La Fe" and Department of Physiology, University of Valencia (Spain) (Accepted 13 December 1988) Key words: Cerebral .blood flow; y-Aminobutyric acid-B receptor; Cerebral artery; Noradrenaline release; Baclofen The possibility that y-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/~g/min) and baclofen (50-100/tg/min) into the internal maxillary artery. Picrotoxin (3 mg) did not change the inhibitory effect of GABA. Exogenously administered noradrenaline (1-9/~g) and tyramine (50-500/lg) 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-~ 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 [SH]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. INTRODUCTION It has been suggested that the central neurotran- smitter y-aminobutyric acid (GABA) participates in the regulation of cerebral blood flow. The enzymes involved in GABA metabolism (glutamate decar- boxylase and GABA-transaminase) have been found in association with the cerebral vasculature 19'2°'37"4°. The existence of postsynaptic receptors that mediate a direct vasodilatory effect of GABA (GABA-A receptors) in the cerebral vasculature seems to be well established: (1) GABA-receptors have been identified mediating dilatation in bovine 23, cat and dog 13'16 and rabbit 5 isolated cerebral arteries; (2) the perivascular microinjection of GABA significantly increased the pial arteriolar caliber32; and (3) the potent GABA-A receptor agonist muscimol pro- duced significant increase in blood flow of cortical brain regions 14. On the other hand, recent experi- mental evidence suggests that GABA can affect sympathetic neurotransmission by acting on presyn- aptic GABA-B receptors in rabbit pulmonary artery 35, rabbit basilar artery 5, rabbit ear artery 3° and bovine ovarian follicle 22. Previous data from our laboratory demonstrated that GABA, directly administered into the cerebral circulation in unanesthetized goats, increases total cerebral blood flow acting on specific GABA-A receptors 2. The aim of the present study was to investigate the possibility that GABA could inter- fere with the adrenergic neurotransmission in the cerebrovascular bed. To achieve this, 3 experimental approaches were used: measurement of cerebral blood flow in anesthetized goats; recording of Correspondence: E. Alborch, Centro de Investigaci6n, Hospital 'La Fe', Avda de Campanar 21, 46009-Valencia, Spain. 0006-8993/89/$03.50 I~ 1989 Elsevier Science Publishers B.V. (Biomedical Division)