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An angiotensin II type 1 receptor blocker can preserve endothelial function and attenuate brain ischemic damage in spontaneously hypertensive rats
Author(s) -
Oyama Naoki,
Yagita Yoshiki,
Sasaki Tsutomu,
OmuraMatsuoka Emi,
Terasaki Yasukazu,
Sugiyama Yukio,
Sakoda Saburo,
Kitagawa Kazuo
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22441
Subject(s) - hydralazine , enos , olmesartan , medicine , endocrinology , spontaneously hypertensive rat , ischemia , blood pressure , cerebral blood flow , endothelial dysfunction , nitric oxide , pharmacology , nitric oxide synthase
Hypertension reduces endothelial nitric oxide synthase (eNOS) expression and leads to endothelial dysfunction. However, few studies have demonstrated the influences of hypertension on eNOS function in the cerebral cortex. The present study investigates the influences of hypertension on endothelial function in the cerebral cortex and the protective effects of antihypertensive agents against brain ischemia through the preservation of endothelial function. Five‐ and ten‐week‐old male Wistar rats and spontaneously hypertensive rats (SHR) were used for experiments. Five‐week‐old SHR received olmesartan, hydralazine, or vehicle for 5 weeks in drinking water. eNOS activation in the cerebral cortex was evaluated by analyzing levels of total and Ser 1177 ‐phosphorylated eNOS protein by Western blot. Blood pressure of 10‐week‐old SHR without treatment was clearly high, and the ratio of phospho‐eNOS/total eNOS protein was significantly low. Five‐week treatment with olmesartan or hydralazine suppressed the elevation of blood pressure and the reduction of phosphorylated eNOS‐Ser 1177 in SHR, and olmesartan was more effective in maintaining phosphorylation of eNOS‐Ser 1177 than hydralazine. To assess the contribution of eNOS to maintaining cerebral blood flow (CBF), we monitored CBF by laser‐Doppler flowmetry after L‐N 5 ‐(1‐iminoethyl)ornithine (L‐NIO) infusion. CBF response to L‐NIO was preserved in olmesartan‐treated SHR but not in hydralazine‐treated SHR. Furthermore, infarct volume 48 hr after transient focal brain ischemia in olmesartan‐treated SHR was significantly reduced compared with vehicle‐treated SHR. These findings indicate that chronic prehypertensive treatment with olmesartan could attenuate brain ischemic injury through the maintenance of endothelial function in the cerebral cortex in SHR. © 2010 Wiley‐Liss, Inc.