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Usage Information

Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease
Masayo Koide, … , Adam S. Greenstein, Mark T. Nelson
Masayo Koide, … , Adam S. Greenstein, Mark T. Nelson
Published August 5, 2021
Citation Information: J Clin Invest. 2021;131(18):e149029. https://doi.org/10.1172/JCI149029.
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Concise Communication Neuroscience Vascular biology

Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease

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Abstract

Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.1. Despite similar efficacy in reducing blood pressure, amlodipine, a voltage-dependent calcium-channel blocker, prevented hypertension-related damage to functional hyperemia whereas losartan, an angiotensin II type 1 receptor blocker, did not. We attribute this drug class effect to losartan-induced aldosterone breakthrough, a phenomenon triggered by pharmacological interruption of the renin-angiotensin pathway leading to elevated plasma aldosterone levels. This hypothesis is supported by the finding that combining losartan with the aldosterone receptor antagonist eplerenone prevented the hypertension-related decline in functional hyperemia. Collectively, these data suggest Kir2.1 as a possible therapeutic target in vascular dementia and indicate that concurrent mineralocorticoid aldosterone receptor blockade may aid in protecting against late-life cognitive decline in hypertensive patients treated with angiotensin II type 1 receptor blockers.

Authors

Masayo Koide, Osama F. Harraz, Fabrice Dabertrand, Thomas A. Longden, Hannah R. Ferris, George C. Wellman, David C. Hill-Eubanks, Adam S. Greenstein, Mark T. Nelson

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Usage data is cumulative from July 2024 through July 2025.

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Citation downloads 89 0
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Total Views 1,917
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