Renoprotective effects of gamma-aminobutyric acid on ischemia/reperfusion-induced renal injury in rats.

Shuhei Kobuchi, Takuya Shintani, Takahiro Sugiura, Ryosuke Tanaka, Rie Suzuki, Hidenobu Tsutsui, Toshihide Fujii, Mamoru Ohkita, Kazuhide Ayajiki, Yasuo Matsumura, Shuhei Kobuchi, Takuya Shintani, Takahiro Sugiura, Ryosuke Tanaka, Rie Suzuki, Hidenobu Tsutsui, Toshihide Fujii, Mamoru Ohkita, Kazuhide Ayajiki, Yasuo Matsumura

Index: Eur. J. Pharmacol. 623(1-3) , 113-8, (2009)

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Abstract

Enhanced renal sympathetic nerve activity during ischemic period and the renal venous norepinephrine overflow after reperfusion play important roles in the development of ischemic acute kidney injury. We investigated the effect of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter mainly in the central nervous system, on ischemia/reperfusion-induced acute kidney injury in anesthetized rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45min followed by reperfusion 2weeks after the contralateral nephrectomy. Intravenous injection of GABA (10 and 50micromol/kg) to ischemic acute kidney injury rats dose-dependently suppressed the enhanced renal sympathetic nerve activity during the renal ischemia, the renal venous norepinephrine overflow after reperfusion and attenuated the ischemia/reperfusion-induced renal dysfunction with histological damage. Intravenous injection of CGP52432 (0.1micromol/kg), a selective GABA(B) receptor antagonist, eliminated the preventive effect by GABA (50micromol/kg) on ischemic acute kidney injury. In contrast, intravenous injection of baclofen (1micromol/kg), a selective GABA(B) receptor agonist, attenuated the ischemia/reperfusion-induced renal injury equivalent to GABA (50micromol/kg). These results indicate that GABA prevents the development of ischemia/reperfusion-induced acute kidney injury presumably via GABA(B) receptor, by suppressing the enhanced renal sympathetic nerve activity during ischemia and the increased norepinephrine overflow from renal sympathetic nerve ending.