Exaggeration of Focal Cerebral Ischemia in Transgenic Mice Carrying Human Renin and Human Angiotensinogen Genes

被引：57

作者：

Inaba, Shinji ^{[1
,2
]}

Iwai, Masaru ^{[1
]}

Tomono, Yumiko ^{[1
]}

Senba, Izumi ^{[1
]}

Furuno, Megumi ^{[1
]}

Kanno, Harumi ^{[1
]}

Okayama, Hideki ^{[2
]}

Mogi, Masaki ^{[1
]}

Higaki, Jitsuo ^{[2
]}

Horiuchi, Masatsugu ^{[1
]}

机构：

[1] Ehime Univ, Grad Sch Med, Dept Mol Cardiovasc Biol & Pharmacol, Shitsukawa, Ehime, Japan

[2] Ehime Univ, Grad Sch Med, Dept Integrated Med & Informat, Shitsukawa, Ehime, Japan

来源：

STROKE | 2009年 / 40卷 / 02期

关键词：

angiotensin; brain infarction; hypertension; receptors; SPONTANEOUSLY HYPERTENSIVE-RATS; TYPE-2 RECEPTOR STIMULATION; CENTRAL-NERVOUS-SYSTEM; BLOOD-FLOW; ARTERY OCCLUSION; SUPEROXIDE-PRODUCTION; OXIDATIVE STRESS; NAD(P)H OXIDASE; II INFUSION; BRAIN;

D O I：

10.1161/STROKEAHA.108.519801

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and Purpose-We examined the possibility that activation of the human brain renin-angiotensin system is involved in enhancement of ischemic brain damage using chimeric transgenic mice with human renin (hRN) and human angiotensinogen (hANG) genes. Methods-Chimeric (hRN/hANG-Tg) mice were generated by mating of hRN and hANG transgenic mice. Permanent occlusion of the middle cerebral artery (MCA) by an intraluminal filament technique induced focal ischemic brain lesions. Results-hRN/hANG-Tg mice showed higher angiotensin II levels in the plasma and brain. The ischemic brain area at 24 hours after MCA occlusion was significantly enlarged in hRN/hANG-Tg mice with an enhanced neurological deficit compared to that in wild-type, hRN-Tg and hANG-Tg mice. The reduction of cerebral blood flow in the periphery region of the MCA territory after MCA occlusion was markedly exaggerated in hRN/hANG-Tg mice. Superoxide anion production in the brain and arteries was also increased significantly in hRN/hANG-Tg mice even before MCA occlusion and was further enhanced after MCA occlusion. Treatment with an AT(1) receptor blocker, valsartan (3.0 mg/kg per day), for 2 weeks significantly reduced the ischemic brain area and improved the neurological deficit after MCA occlusion in hRN/hANG-Tg mice, similar to those in wild-type, hRN-Tg, and hANG-Tg mice, with restoration of cerebral blood flow in the peripheral region and decreases in superoxide anion production and blood pressure. Conclusions-These results indicate that activation of the human renin-angiotensin system exaggerates ischemic brain damage mainly through stimulation of the AT1 receptor and marked reduction of cerebral blood flow and enhanced oxidative stress. (Stroke. 2009;40:597-603.)

引用

页码：597 / 603

页数：7

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