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Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats.

Authors :
Lupachyk S
Watcho P
Shevalye H
Vareniuk I
Obrosov A
Obrosova IG
Yorek MA
Source :
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2013 Aug 01; Vol. 305 (3), pp. E396-404. Date of Electronic Publication: 2013 Jun 04.
Publication Year :
2013

Abstract

Evidence for an important role for Na(+)/H(+) exchangers in diabetic complications is emerging. The aim of this study was to evaluate whether Na(+)/H(+) exchanger 1 inhibition reverses experimental peripheral diabetic neuropathy. Control and streptozotocin-diabetic rats were treated with the specific Na(+)/H(+) exchanger 1 inhibitor cariporide for 4 wk after 12 wk without treatment. Neuropathy end points included sciatic motor and sensory nerve conduction velocities, endoneurial nutritive blood flow, vascular reactivity of epineurial arterioles, thermal nociception, tactile allodynia, and intraepidermal nerve fiber density. Advanced glycation end product and markers of oxidative stress, including nitrated protein levels in sciatic nerve, were evaluated by Western blot. Rats with 12-wk duration of diabetes developed motor and sensory nerve conduction deficits, thermal hypoalgesia, tactile allodynia, and intraepidermal nerve fiber loss. All these changes, including impairment of nerve blood flow and vascular reactivity of epineurial arterioles, were partially reversed by 4 wk of cariporide treatment. Na(+)/H(+) exchanger 1 inhibition was also associated with reduction of diabetes-induced accumulation of advanced glycation endproduct, oxidative stress, and nitrated proteins in sciatic nerve. In conclusion, these findings support an important role for Na(+)/H(+) exchanger 1 in functional, structural, and biochemical manifestations of peripheral diabetic neuropathy and provide the rationale for development of Na(+)/H(+) exchanger 1 inhibitors for treatment of diabetic vascular and neural complications.

Details

Language :
English
ISSN :
1522-1555
Volume :
305
Issue :
3
Database :
MEDLINE
Journal :
American journal of physiology. Endocrinology and metabolism
Publication Type :
Academic Journal
Accession number :
23736542
Full Text :
https://doi.org/10.1152/ajpendo.00186.2013