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Endothelium, the Blood–Brain Barrier, and Hypertension

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Hypertension and the Brain as an End-Organ Target

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Abstract

This chapter summarizes concepts regarding the effects of hypertension on the cerebral circulation. In relation to end-organ effects, the brain is one of the organs most significantly affected by chronic elevations in arterial pressure. Hypertension is a leading risk factor for cerebrovascular disease, stroke, and cognitive decline. Endothelial cells are a target of hypertension. These cells are normally key determinants of vascular tone, while also protecting against thrombosis and abnormal vascular growth. The impact of acute and chronic hypertension is outlined with emphasis on changes in the biology of the signaling molecule nitric oxide and the role that oxidative stress plays in these changes. The importance of NADPH oxidase and other mechanisms that promote oxidative stress are presented. As part of the discussion, there is an overview regarding vascular alterations in various genetic and pharmacological models of hypertension. Effects of the renin-angiotensin system and angiotensin-II are highlighted. Endothelial cells are also the site of the blood–brain barrier (BBB). The molecular organization of the BBB is summarized along with key changes that occur in response to acute and chronic hypertension. Lastly, the clinical impact of these changes is discussed.

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Acknowledgments

Work summarized in this chapter was supported by research grants from the National Institute of Health (HL-38901, NS-24621, HL-62984, and HL-113863), the Department of Veteran’s Affair’s (BX001399), and the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Cerebral Small Vessel Disease in the Brain). TMD was the recipient of an Overseas Post-doctoral Fellowship from the National Health and Medical Research Council of Australia (1053786). RP received a North Shore University Hospital Chair of Research Award from the Brain Aneurysm Foundation.

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    Authors and Affiliations

    1. Department of Internal Medicine, Francois M. Abboud Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

      T. Michael De Silva, Ricardo A. Peña Silva & Frank M. Faraci Ph.D.

    2. Department of Pharmacology, Francois M. Abboud Cardiovascular Center, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

      T. Michael De Silva & Ricardo A. Peña Silva

    3. College of Medicine, Universidad de los Andes, Bogota, Colombia

      Ricardo A. Peña Silva

    4. Iowa City Veterans Affairs Healthcare System, Iowa City, IA, 52242, USA

      Frank M. Faraci Ph.D.

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    Correspondence to Frank M. Faraci Ph.D. .

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    1. Faculty of Medicine, Université de Montréal, Montréal, Canada

      Hélène Girouard

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    De Silva, T.M., Silva, R.A.P., Faraci, F.M. (2016). Endothelium, the Blood–Brain Barrier, and Hypertension. In: Girouard, H. (eds) Hypertension and the Brain as an End-Organ Target. Springer, Cham. https://doi.org/10.1007/978-3-319-25616-0_8

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