In:
Clinical and Experimental Pharmacology and Physiology, Wiley, Vol. 42, No. 3 ( 2015-03), p. 278-286
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0305-1870
,
1440-1681
DOI:
10.1111/cep.2015.42.issue-3
DOI:
10.1111/1440-1681.12350
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2020033-X
SSG:
15,3
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