title: Protection against ischemic stroke damage by synergistic treatment with amlodipine plus atorvastatin in Zucker metabolic rat.
abstract: Ischemic stroke is a major neurologic disorder and a leading cause of disability and death in the world. We compared neuroprotective effects of single or combination therapy of amlodipine (AM) and atorvastatin (AT) in such a metabolic syndrome model Zucker rat. The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28days, and physical and serum parameters were analyzed, then 90min of transient middle cerebral artery occlusion (tMCAO), was performed followed by immunohistochemical analyses at 24h. Without affecting serum levels of lipids, adiponectin, and leptin, the combination therapy of AM plus AT ameliorated the post-ischemic brain weight increase. The single treatment with AM or AT itself exerted neuroprotective effects with reducing inductions of MMP-9 and AT2R, as well as with preserving collagen IV, and the combination therapy of AM plus AT showed a further synergistic benefit against acute ischemic neural damages. Single AT was more protective on these 3 molecules than single AM at this time point of 24h after tMCAO. Thus, the combination therapy with AM plus AT extended the neuroprotectives effect of single treatment with AM or AT on a part of neurovascular unit and a hypertension-related receptor.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kawai
authors.forename: Shoko
authors.initials: S
authors.lastname: Deguchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Omote
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tohru
authors.initials: T
authors.lastname: Matsuura
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000069059:Atorvastatin; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011924:Rats, Zucker; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002121:Calcium Channel Blockers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D011758:Pyrroles; D017311:Amlodipine; D000069059:Atorvastatin