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Effect of Angiotensin II on gene expression in SHRSP cerebral microcapillaries

ABSTRACT: Renin-angiotensin system (RAS) inhibition reduces stroke and improves brain capillary integrity in stroke prone spontaneously hypertensive rats (SHRSP). We tested the hypothesis that treatment with an angiotensin II receptor subtype 1 (AT1R) antagonist has different effects, compared to an angiotensin converting enzyme (ACE) inhibitor, on gene expression in blood-brain barrier (BBB) capillaries. Six weeks old SHRSP were treated with either olmesartan (4 mg/kg, n=20), lisinopril (6 mg/kg , n=20) or remained untreated (n=20). Blood pressure was controlled by tail-cuff measurement. After 5 weeks the animals were sacrificed and cerebral capillaries were isolated. mRNA was extracted and analyzed with rat GeneChip DNA arrays. Additionally, brain histology and monocyte/macrophage infiltrates were determined. Both treatments similarly reduced neurological signs of stroke, stroke mortality, and monocyte/macrophage infiltration, compared to controls. Blood pressure was not influenced significantly by both drugs. We found 42 transcripts that were regulated by both treatments in the same manner. These genes were mostly related to inflammation. We also observed 39 differentially expressed genes between the two treatment groups that typically contribute to cell growth and differentiation. This study demonstrates that, despite similar effects on cerebral pathology and outcome, ACE inhibition and AT1R blockade have distinct molecular effects on gene expression in BBB capillaries. Keywords = angiotensin II Keywords = gene expression Keywords = microarrays Keywords = brain capillaries Keywords = SHRSP Keywords = olmesartan Keywords = lisinopril Keywords: other

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE1548 | GEO | 2004/08/31

SECONDARY ACCESSION(S): PRJNA89945

REPOSITORIES: GEO

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Transcription profiling of stroke-prone spontaneously hypertensive (SHRSP) rats treated with either an angiotensin II receptor (AT1R) antagonist or an angiotensin converting enzyme (ACE) inhibitor

Project description:Renin-angiotensin system (RAS) inhibition reduces stroke and improves brain capillary integrity in stroke prone spontaneously hypertensive rats (SHRSP). We tested the hypothesis that treatment with an angiotensin II receptor subtype 1 (AT1R) antagonist has different effects, compared to an angiotensin converting enzyme (ACE) inhibitor, on gene expression in blood-brain barrier (BBB) capillaries. Six weeks old SHRSP were treated with either olmesartan (4 mg/kg, n=20), lisinopril (6 mg/kg , n=20) or remained untreated (n=20). Blood pressure was controlled by tail-cuff measurement. After 5 weeks the animals were sacrificed and cerebral capillaries were isolated. mRNA was extracted and analyzed with rat GeneChip DNA arrays. Additionally, brain histology and monocyte/macrophage infiltrates were determined. Both treatments similarly reduced neurological signs of stroke, stroke mortality, and monocyte/macrophage infiltration, compared to controls. Blood pressure was not influenced significantly by both drugs. We found 42 transcripts that were regulated by both treatments in the same manner. These genes were mostly related to inflammation. We also observed 39 differentially expressed genes between the two treatment groups that typically contribute to cell growth and differentiation. This study demonstrates that, despite similar effects on cerebral pathology and outcome, ACE inhibition and AT1R blockade have distinct molecular effects on gene expression in BBB capillaries.

2007-10-31 | E-GEOD-1548 | biostudies-arrayexpress

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