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

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 γ-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 45 min followed by reperfusion 2 weeks after the contralateral nephrectomy. Intravenous injection of GABA (10 and 50 μmol/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 (0.1 μmol/kg), a selective GABAB receptor antagonist, eliminated the preventive effect by GABA (50 μmol/kg) on ischemic acute kidney injury. In contrast, intravenous injection of baclofen (1 μmol/kg), a selective GABAB receptor agonist, attenuated the ischemia/reperfusion-induced renal injury equivalent to GABA (50 μmol/kg). These results indicate that GABA prevents the development of ischemia/reperfusion-induced acute kidney injury presumably via GABAB receptor, by suppressing the enhanced renal sympathetic nerve activity during ischemia and the increased norepinephrine overflow from renal sympathetic nerve ending.