Candesartan reduces superoxide production after global cerebral ischemia.
Excessive superoxide production after cerebral ischemia is known to mediate neuronal injury. Angiotensin II type 1 receptor activation results in production of superoxide, but whether angiotensin II type 1 receptor blockade prevents production of superoxide and subsequent neuronal injury after ischemia remains unclear. Normotensive rats received the angiotensin II type 1 receptor blocker, candesartan or only vehicle before induction of global cerebral ischemia. Approximately 30% of the hippocampal CA1 neurons survived in candesartan-treated animals, whereas only 2% of neurons survived in vehicle-treated animals. Superoxide production was significantly less in these vulnerable neurons in candesartan-treated animals than in vehicle-treated animals. Angiotensin II type 1 receptor may have an essential role in superoxide production and subsequent injury in vulnerable neurons after global cerebral ischemia.
Sugawara
Taku
T
Department of Neurosurgery, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. taku@nsg.med.akita-u.ac.jp
Kinouchi
Hiroyuki
H
Oda
Masaya
M
Shoji
Hidehiko
H
Omae
Tomoya
T
Mizoi
Kazuo
K
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018696:Neuroprotective Agents; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D013481:Superoxides; C081643:candesartan