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

Shinsei Fujimura, Hironori Shimakage, Hideki Tanioka, Makoto Yoshida, Mizue Suzuki-Kusaba, Hiroaki Hisa, Susumu Satoh

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36 Citations (Scopus)

Abstract

1. We examined effects of γ-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 μM) 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 μM) 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 μM). 4. The selective GABA(B) antagonist 2-hydroxysaclofen (50 μM), but not the selective GABA(A) antagonist bicuculline (50 μM), abolished the inhibitory effects of GABA (10 μM) on the RNS-induced responses. 5. The selective α2-adrenoceptor antagonist rauwolscine (10 μM ) enhanced the RNS-induced responses. GABA (3, 10 and 100 μM) potently attenuated the RNS-induced increases in PP by 40-60% (P < 0.01) and NA efflux by 20-50% (P < 0.01) in the presence of rauwolscine. 6. Prazosin (10 and 30 nM) suppressed the RNS-induced increases in PP by about 70-80%. Neither rauwolscine (10 nM) nor GABA (10 μM) 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.

Original languageEnglish
Pages (from-to)109-114
Number of pages6
JournalBritish Journal of Pharmacology
Volume127
Issue number1
DOIs
Publication statusPublished - 1999

Keywords

  • GABA(B) receptor
  • Noradrenaline release
  • Rat kidney
  • Sympathetic nerves
  • γ-aminobutyric acid (GABA)

ASJC Scopus subject areas

  • Pharmacology

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