Neuroprotective effects of candesartan against cerebral ischemia in spontaneously hypertensive rats.
The cerebral protective effects of 4-week treatment with candesartan (0.3, 1, 3 mg/kg/day) and ramipril (0.5, 1.5, 5 mg/kg/day) were examined in spontaneous hypertensive rats 24 h after middle cerebral artery occlusion. We found that both candesartan and ramipril could reduce the infarct volume and neurological deficit scores compared with control. Importantly, the neuroprotective effects of candesartan (1 mg/kg/day) were abolished by PD123319 (an AT2 receptor antagonist, 10 mg/kg/day). AT1 receptor gene expression was downregulated while AT2 receptor gene expression was upregulated by candesartan. It is concluded that candesartan appears to provide beneficial effects against stroke in spontaneous hypertensive rats in three ways: AT1 receptor antagonism, downregulation of AT1 receptor expression and upregulation of AT2 receptor expression.
Lu
Qing
Q
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Zhu
Yi-Zhun
YZ
Wong
Peter T-H
PT
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure; D001835:Body Weight; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015870:Gene Expression / Q000187:drug effects; D006339:Heart Rate; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D013777:Tetrazoles / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D018696:Neuroprotective Agents; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; C073402:PD 123319; C081643:candesartan