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  Multimodal Imaging in Rats Reveals Impaired Neurovascular Coupling in Sustained Hypertension

Calcinaghi, N., Wyss, M., Jolivet, R., Singh, A., Keller, A., Winnik, S., et al. (2013). Multimodal Imaging in Rats Reveals Impaired Neurovascular Coupling in Sustained Hypertension. Stroke, 44(7), 1957-1964. doi:10.1161/STROKEAHA.111.000185.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-001A-1406-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-3F03-6
Genre: Journal Article

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Calcinaghi, N, Author
Wyss, MT, Author
Jolivet, R, Author
Singh, A, Author
Keller, AL1, 2, Author              
Winnik, S, Author
Fritschy, J-M, Author
Buck, A, Author
Matter, CM, Author
Weber, B, Author              
Affiliations:
1Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497798              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: BACKGROUND AND PURPOSE: Arterial hypertension is an important risk factor for cerebrovascular diseases, such as transient ischemic attacks or stroke, and represents a major global health issue. The effects of hypertension on cerebral blood flow, particularly at the microvascular level, remain unknown. METHODS: Using the spontaneously hypertensive rat (SHR) model, we examined cortical hemodynamic responses on whisker stimulation applying a multimodal imaging approach (multiwavelength spectroscopy, laser speckle imaging, and 2-photon microscopy). We assessed the effects of hypertension in 10-, 20-, and 40-week-old male SHRs and age-matched male Wistar Kyoto rats (CTRL) on hemodynamic responses, histology, and biochemical parameters. In 40-week-old animals, losartan or verapamil was administered for 10 weeks to test the reversibility of hypertension-induced impairments. RESULTS: Increased arterial blood pressure was associated with a progressive impairment in functional hyperemia in 20- and 40-week-old SHRs; baseline capillary red blood cell velocity was increased in 40-week-old SHRs compared with age-matched CTRLs. Antihypertensive treatment reduced baseline capillary cerebral blood flow almost to CTRL values, whereas functional hyperemic signals did not improve after 10 weeks of drug therapy. Structural analyses of the microvascular network revealed no differences between normo- and hypertensive animals, whereas expression analyses of cerebral lysates showed signs of increased oxidative stress and signs of impaired endothelial homeostasis upon early hypertension. CONCLUSIONS: Impaired neurovascular coupling in the SHR evolves upon sustained hypertension. Antihypertensive monotherapy using verapamil or losartan is not sufficient to abolish this functional impairment. These deficits in neurovascular coupling in response to sustained hypertension might contribute to accelerate progression of neurodegenerative diseases in chronic hypertension.

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 Dates: 2013-07
 Publication Status: Published in print
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 Identifiers: DOI: 10.1161/STROKEAHA.111.000185
BibTex Citekey: CalcinaghiWJSKWFBMW2013
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Title: Stroke
Source Genre: Journal
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Pages: - Volume / Issue: 44 (7) Sequence Number: - Start / End Page: 1957 - 1964 Identifier: -