Comparison of inhibitory action of candesartan and enalapril on brain ischemia through inhibition of oxidative stress.
The effects of an angiotensin II type 1 (AT1) receptor blocker (ARB) on ischemic brain damage induced by middle cerebral artery (MCA) occlusion were compared with those of an angiotensin converting enzyme (ACE) inhibitor. Treatment of male C57BL/6J mice with an ARB, candesartan, reduced the brain ischemic area and neurological deficit after MCA occlusion at a non-hypotensive dose. In contrast, an ACE inhibitor, enalapril, did not reduce the brain ischemic area, and neurological deficit even at a hypotensive dose. Candesartan improved the reduction of brain surface blood flow after MCA occlusion, and inhibited the increase in superoxide production both in the cortex and brain arterial wall at non-hypotensive and hypotensive doses. However, enalapril did not affect the changes in blood flow and superoxide production in the brain after MCA occlusion. AT2 receptor expression in the ischemic area was increased at 3 h after MCA occlusion by pretreatment with candesartan, but not that with enalapril. AT1 receptor expression was neither affected by candesartan nor by enalapril. These results suggest that candesartan attenuated ischemic brain damage, at least partly, through inhibition of oxidative stress.
Hamai
Meiko
M
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.
Iwai
Masaru
M
Ide
Ayumi
A
Tomochika
Hirokazu
H
Tomono
Yumiko
Y
Mogi
Masaki
M
Horiuchi
Masatsugu
M
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D006649:Histocompatibility Antigens / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D013778:Tetrazolium Salts
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D006649:Histocompatibility Antigens; D012333:RNA, Messenger; D013777:Tetrazoles; D013778:Tetrazolium Salts; C070850:transplantation antigen P91A, mouse; D013481:Superoxides; D004656:Enalapril; C009591:triphenyltetrazolium; C081643:candesartan