Effects of GABA on noradrenaline release and vasoconstriction induced by renal nerve stimulation in isolated perfused rat kidney

1 We examined effects of gamma-aminobutyric acid (GABA) on vasoconstriction and noradrenaline (NA) release induced by electrical renal nerve stimulation (RNS) in the isolated pump-perfused rat kidney. 2 RNS (1 and 2 Hz for 2.5 min each, 0.5-ms duration, supramaximal voltage) increased renal perfusion pressure (PP) and renal NA efflux. GABA (3, 10 and 100 mu M) attenuated the RNS-induced increases in PP by 10-40% (P<0.01) and NA efflux by 10-30% (P<0.01). GABA did not affect exogenous NA (40 and 60 nM)-induced increases in PP. 3 The selective GABA(B) agonist baclofen (3, 10 and 100 mu M) also attenuated the RNS-induced increases in PP and NA efflux, whereas the RNS-induced responses were relatively resistant to the selective GABA(A) agonist muscimol (3, 10 and 100 mu M). 4 The selective GABA(B) antagonist 2-hydroxysaclofen (50 mu M), but not the selective GABA(A) antagonist bicuculline (50 mu M), abolished the inhibitory effects of GABA (10 mu M) on the RNS-induced responses. 5 The selective alpha(2)-adrenoceptor antagonist rauwolscine (10nM) enhanced the RNS-induced responses. GABA (3, 10 and 100 mu M) potently attenuated the RNS-induced increases in PP by 30-60% (P<0.01) and NA efflux; by 20-50% (P<0.01) in the presence of rauwolscine. 6 Prazosin (10 and 30 nh I) suppressed the RNS-induced increases in PP by about 70-80%. Neither rauwolscine (10 nM) nor GABA (10 mu M) suppressed the residual prazosin-resistant PP response. 7 These results suggest that GABA suppresses sympathetic neurotransmitter release via presynaptic GABA(B) receptors, and thereby attenuates adrenergically induced vasoconstriction in the rat kidney.