Renoprotective effects of gamma-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 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.
Kobuchi
Shuhei
S
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Shintani
Takuya
T
Sugiura
Takahiro
T
Tanaka
Ryosuke
R
Suzuki
Rie
R
Tsutsui
Hidenobu
H
Fujii
Toshihide
T
Ohkita
Mamoru
M
Ayajiki
Kazuhide
K
Matsumura
Yasuo
Y
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D007668:Kidney / Q000098:blood supply / Q000294:innervation / Q000473:pathology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D007683:Kidney Tubular Necrosis, Acute / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000097:blood; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000378:metabolism*
D001596:Benzylamines; D018755:GABA Agonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; C083008:CGP 52432; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D009638:Norepinephrine