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Mechanisms underlying the renoprotective effect of GABA against ischaemia/reperfusion‐induced renal injury in rats
Author(s) -
Kobuchi Shuhei,
Tanaka Ryosuke,
Shintani Takuya,
Suzuki Rie,
Tsutsui Hidenobu,
Ohkita Mamoru,
Matsumura Yasuo,
Ayajiki Kazuhide
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12350
Subject(s) - bicuculline , medicine , gabaa receptor , ischemia , kidney , agonist , pharmacology , stimulation , acute kidney injury , antagonist , receptor , endocrinology
Excitation of the renal sympathetic nervous system is important for the development of ischaemic acute kidney injury ( AKI ) in rats. We reported that intravenous treatment with GABA has preventive effects against ischaemia/reperfusion (I/R)‐induced renal dysfunction with histological damage in rats; however, the mechanisms underlying these effects on renal injury remain unknown. Thus, the aim of the present study was to clarify how GABA mechanistically affects ischaemic AKI in rats. Ischaemic AKI was induced in rats by clamping the left renal artery and vein for 45 min and then reperfusing the kidney to produce I/R‐induced injury. Treatment with the GABA B receptor antagonist CGP 52432 (100 nmol/kg, i.v., or 1 nmol/kg, i.c.v.) abolished the suppressive effects of 50 μ mol/kg, i.v., GABA on enhanced renal sympathetic nerve activity ( RSNA ) during ischaemia, leading to elimination of the renoprotective effects of GABA . Intracerebroventricular treatment with 0.5 μ mol/kg GABA or i.v. treatment with 1 μ mol/kg baclofen, a selective GABA B receptor agonist, prevented the I/R‐induced renal injury equivalent to i.v. treatment with GABA . Conversely, i.v. treatment with 10 μ mol/kg bicuculline, a GABA A receptor antagonist, failed to affect the preventive effects of GABA against ischaemic AKI . We therefore concluded that GABA B receptor stimulation in the central nervous system, rather than peripheral GABA B receptor stimulation, mediates the preventive effect of GABA against ischaemic AKI by suppressing the enhanced RSNA induced by renal ischaemia.