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Role of Oxidative Stress in Hypertension

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Studies on Atherosclerosis

Abstract

Oxidative stress, defined as an increase in steady-state levels of superoxide, is involved in the pathogenesis of several cardiovascular diseases. Hypertension is a major risk factor for cardiovascular diseases, and there exists much experimental support for a role of oxidative stress in hypertension, often in association with vascular abnormalities including endothelial dysfunction. Vascular NADPH oxidases (Nox) are by far the most researched topic amongst the sources of reactive oxygen species (ROS) in hypertension, and are thought to be a predominant underlying cause of oxidative stress in hypertension. The purpose of this chapter is to discuss the involvement of oxidative stress in association with vascular abnormalities in animal models of hypertension, with a particular emphasis on evidence for involvement of Nox in three commonly studied models: angiotensin II (Ang II)-induced hypertension, mineralocorticoid-dependent hypertension and the spontaneously hypertensive rat (SHR). Antioxidant defence mechanisms (i.e. superoxide dismutases [SOD]’s and glutathione peroxidases [GPx’s]) may limit vascular oxidative stress, thus experimental evidence discussing their likely protection against vascular oxidative stress and hypertension will be discussed. Recent concepts regarding the link between oxidative stress, the immune system and hypertension will also be covered, and finally we will briefly address clinical data providing an association between oxidative stress and hypertension, in particular the link between genetic abnormalities and oxidative stress in hypertension.

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Abbreviations

Ang II:

Angiotensin II

AT1R:

Angiotensin II type 1 receptor

Atox-1:

Antioxidant-1

CD40L:

CD40 ligand

COX:

Cyclooxygenase

CuZnSOD:

Copper-zinc superoxide dismutase

DOCA:

Deoxycorticosterone acetate

DUOX:

Dual oxidase

ECSOD:

Extracellular superoxide dismutase

eNOS:

Endothelial nitric oxide synthase

G6PD:

Glucose-6-phosphate dehydrogenase

GPx:

Glutathione peroxidase

ICAM-1:

Intracellular adhesion molecule-1

MnSOD:

Manganese superoxide dismutase

NO:

Nitric oxide

PPARβ:

Peroxisome proliferator-activated receptor beta

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SHR:

Spontaneously hypertensive rat

SHRSP:

Stroke-prone spontaneously hypertensive rat

siRNA:

Small-interfering RNA

SOD:

Superoxide dismutase

TNFα:

Tumour necrosis factor alpha

VCAM-1:

Vascular cell adhesion molecule-1

WKY:

Wistar-Kyoto

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Authors and Affiliations

  1. Department of Pharmacology, Monash University, Building 13E, Wellington Rd, Clayton, VIC, 3800, Australia

    Sophocles Chrissobolis Ph.D., Quynh N. Dinh, Grant R. Drummond & Christopher G. Sobey

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  1. Sophocles Chrissobolis Ph.D.
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  2. Quynh N. Dinh
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  3. Grant R. Drummond
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  4. Christopher G. Sobey
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Correspondence to Sophocles Chrissobolis Ph.D. .

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Editors and Affiliations

  1. Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA

    Martin Rodriguez-Porcel

  2. University of Mississippi, Jackson, Mississippi, USA

    Alejandro R. Chade

  3. Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA

    Jordan D. Miller

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Chrissobolis, S., Dinh, Q.N., Drummond, G.R., Sobey, C.G. (2017). Role of Oxidative Stress in Hypertension. In: Rodriguez-Porcel, M., Chade, A., Miller, J. (eds) Studies on Atherosclerosis. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Boston, MA. https://doi.org/10.1007/978-1-4899-7693-2_4

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