Mechanism underlying γ-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats

We examined the effects of gamma-aminobutyric acid (GABA) on the blood pressure in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. A single oral administration (0.5 mg/kg) significantly lowered the systolic blood pressure in spontaneously hypertensive rats, but not in normotensive rats. In the mesenteric arterial bed, the perivascular nerve stimulation-induced increase in perfusion pressure and noradrenaline release were significantly inhibited by GABA in spontaneously hypertensive rats, but not in normotensive rats, and attenuated by the selective GABA(B) receptor agonist, baclofen, but not by the selective GABA(A) receptor agonist muscimol. The inhibitory effects of GABA on the perivascular nerve stimulation-induced increase in perfusion pressure and noradrenaline release were completely antagonized by the selective GABA(B) receptor antagonist, saclofen, but not by the selective GABA(A) receptor antagonist, bicuculline. These results suggest that, in spontaneously hypertensive rats, GABA has an antihypertensive effect due to its inhibition of noradrenaline release from sympathetic nerves in the mesenteric arterial bed via presynaptic GABA(B) receptors. (C) 2002 Elsevier Science B.V. All rights reserved.