Trophic effect of olmesartan, a novel AT1R antagonist, on spinal motor neurons in vitro and in vivo.
Olmesartan is a novel compound which has been shown to exhibit various neuropharmacological effects. For the purpose of clarifying the effect of Olmesartan on spinal motor neurons, we studied the following tests. We studied the effect in vitro of Olmesartan on neurite outgrowth and choline acetyltransferase (ChAT) activity in primary explant cultures of ventral spinal cord (VSCC) of fetal rats. Olmesartan-treated VSCC, compared with control VSCC, had a significant neurite outgrowth and increased activity of ChAT. The effect was dose-related in neurite outgrowth. However, there was no relationship between activity of ChAT andgiven doses of Olmesartan. We examined in vivo the effect of Olmesartan on axotomized spinal motor neuron death in the rat spinal cord. After post-natal unilateral section of sciatic nerve, there was approximately a 50% survival of motor neurons in the fourth lumbar segment. In comparison with vehicle, intraperitoneal injection of Olmesartan for consecutive 14 days reduced spinal motor neuron death. There was no relationship between number of surviving neurons and doses of Olmesartan. These in vitro and in vivo studies showed that Olmesartan has a neurotrophic effect on spinal motor neurons. Our data suggest a potential therapeutic use of Olmesartan in treating diseases that involve degeneration and death of motor neurons, such as motor neuropathy and amyotrophic lateral sclerosis.
Fourth Department of Internal Medicine, Toho University Ohashi Hospital, Tokyo, Japan. yaso@med.toho-u.ac.jp
Yasuo
Y
Iwasaki
Yasumitsu
Y
Ichikawa
Osamu
O
Igarashi
Masao
M
Kinoshita
Ken
K
Ikeda
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D007093:Imidazoles / Q000494:pharmacology*; D007511:Ischemia / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000068557:Olmesartan Medoxomil; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism; D012183:Retrograde Degeneration / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D012584:Sciatic Nerve / Q000293:injuries / Q000601:surgery; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; D002795:Choline O-Acetyltransferase