Olmesartan medoxomil ameliorates sciatic nerve regeneration in diabetic rats.
To evaluate the effect of angiotensin II type1 receptor blocker on nerve regeneration delay in diabetic rats, nerve regeneration was monitored by a pinch test on the crushed sciatic nerves of streptozotocin-induced diabetic rats. Nerve regeneration was significantly delayed in diabetic rats and was partly ameliorated by treatment with olmesartan medoxomil (3 mg/kg/day, orally). In the ipsilateral dorsal root ganglia, the mRNA level of insulin-like growth factor-1 and ciliary neurotrophic factor (CNTF) was downregulated, whereas the mRNA level of neurotrophin-3 and CNTF receptor was upregulated. Olmesartan medoxomil significantly enhanced the CNTF expression. These results showed that angiotensin II type1 receptor blocker treatment is effective on nerve regeneration delay in diabetic animals and may provide an effective therapy for clinical diabetic neuropathy.
Biological Research Laboratories II, R&D Division Daiichi-Sankyo Co. Ltd., Tokyo, Japan. nakamura.hiroaki.xn@daiichisankyo.co.jp
Hiroaki
H
Nakamura
Yuki
Y
Domon
Tatsuya
T
Inoue
Naohisa
N
Arakawa
Tomihisa
T
Yokoyama
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism; D000068557:Olmesartan Medoxomil; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000503:physiopathology*; D013311:Streptozocin; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D020934:Ciliary Neurotrophic Factor; D007093:Imidazoles; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D013777:Tetrazoles; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I; D000068557:Olmesartan Medoxomil; C049478:insulin-like growth factor I, Val(59)-