Role of Angiotensin and Oxidative Stress in Essential Hypertension

Romero, J. Carlos; Reckelhoff, Jane F.

doi:10.1161/01.hyp.34.4.943

Cited by 359Renin-Angiotensin System StudiesEicosanoids and Hypertension PharmacologyNitric Oxide and Endothelin Effects

Role of Angiotensin and Oxidative Stress in Essential Hypertension

Romero, J. Carlos, Reckelhoff, Jane F.·1999·Hypertension

DOI 10.1161/01.hyp.34.4.943

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Abstract

In this review, we examine the possibility that small increments in angiotensin II are responsible for an increase in blood pressure and maintenance of hypertension through the stimulation of oxidative stress. A low dose of angiotensin II (2 to 10 ng x kg(-1) x min(-1), which does not elicit an immediate pressor response), when given for 7 to 30 days by continuous intravenous infusion, can increase mean arterial pressure by 30 to 40 mm Hg. This slow pressor response to angiotensin is accompanied by the stimulation of oxidative stress, as measured by a significant increase in levels of 8-iso-prostaglandin F(2alpha) (F(2)-isoprostane). Superoxide radicals and nitric oxide can combine chemically to form peroxynitrite, which can then oxidize arachidonic acid to form F(2)-isoprostanes. F(2)-isoprostanes exert potent vasoconstrictor and antinatriuretic effects. Furthermore, angiotensin II can stimulate endothelin production, which also has been shown to stimulate oxidative stress. In this way, a reduction in the concentration of nitric oxide (which is quenched by superoxide) along with the formation of F(2)-isoprostanes and endothelin could potentiate the vasoconstrictor effects of angiotensin II. We hypothesize that these mechanisms, which underlie the development of the slow pressor response to angiotensin II, also participate in the production of hypertension when circulating angiotensin II levels appear normal, as occurs in many cases of essential and renovascular hypertension.

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Although plasma angiotensin II levels are not consistently elevated in essential hypertension, activation of tissue-specific renin-angiotensin systems, including in brain and blood vessels, is thought to play a role.
“Although plasma levels of ANGII are not consistently elevated in essential hypertension (13), activation of tissue-specific renin-angiotensin systems, including in brain and blood vessels, is thought to play a role (62).”
From Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension (2016) · cites this paper as [13]

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NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases
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Antioxidant Activities and Oxidative Stress Byproducts in Human Hypertension
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The AT 1 -Type Angiotensin Receptor in Oxidative Stress and Atherogenesis
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Increased Oxidative Stress in Experimental Renovascular Hypertension
Lerman, L. O., Nath, K. A., Rodriguez-Porcel, M. G., Krier, J. D., Schwartz, R. S., Claudio Napoli, A., & Romero, J. C. (2001) · Hypertension · doi:10.1161/01.hyp.37.2.541 · Cited by 270 · see citing works
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Is obesity a major cause of chronic kidney disease?
Hall, J. E., Henegar, J. R., Dwyer, T. M., Liu, J., da Silva, A. A., Kuo, J. J., & Tallam, L. (2004) · Advances in Renal Replacement Therapy · doi:10.1053/j.arrt.2003.10.007 · Cited by 264 · see citing works
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Preventing and Experiencing Ischemic Heart Disease as a Woman: State of the Science
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Hypertension in Postmenopausal Women
Lima, R., Wofford, M. R., & Reckelhoff, J. F. (2012) · Current Hypertension Reports · doi:10.1007/s11906-012-0260-0 · Cited by 256 · see citing works
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Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension
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Hypertension: Physiology and Pathophysiology
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Role of Oxidative Stress in the Pathophysiological Mechanism of Erectile Dysfunction
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Malondialdehyde (MDA) and protein carbonyl (PCO) levels as biomarkers of oxidative stress in subjects with familial hypercholesterolemia
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Vitamin D cell signalling in health and disease
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Mitochondria-Derived Reactive Oxygen Species and Vascular MAP Kinases
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Epoxy-Keto Derivative of Linoleic Acid Stimulates Aldosterone Secretion
Goodfriend, T. L., Ball, D. L., Egan, B. M., Campbell, W. B., & Nithipatikom, K. (2004) · Hypertension · doi:10.1161/01.hyp.0000113294.06704.64 · Cited by 205 · see citing works
Role of oxidative stress in angiotensin-induced hypertension
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Animal models of hypertension: An overview
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The AT 1 -Type Angiotensin Receptor in Oxidative Stress and Atherogenesis
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A Mouse Model of Angiotensin II Slow Pressor Response: Role of Oxidative Stress
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Eicosanoid regulation of the renal vasculature
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Postmenopausal Hypertension
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Antihypertensive Effect of Green Coffee Bean Extract on Mildly Hypertensive Subjects
Kozuma, K., TSUCHIYA, S., Kohori, J., Hase, T., & Tokimitsu, I. (2005) · Hypertension Research · doi:10.1291/hypres.28.711 · Cited by 180 · see citing works
Critical Role of Angiotensin II in Excess Salt-Induced Brain Oxidative Stress of Stroke-Prone Spontaneously Hypertensive Rats
Kim‐Mitsuyama, S., Yamamoto, E., Tanaka, T., Zhan, Y., Izumi, Y., Izumiya, Y., Ioroi, T., Wanibuchi, H., & Iwao, H. (2005) · Stroke · doi:10.1161/01.str.0000163084.16505.e3 · Cited by 173 · see citing works
Angiotensin II induced cerebral microvascular inflammation and increased blood–brain barrier permeability via oxidative stress
Zhang, M., Mao, Y., Ramirez, S. H., Tuma, R. F., & Chabrashvili, T. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.09.029 · Cited by 169 · see citing works
Renal Artery Stenosis: A Common, Treatable Cause of Renal Failure?
Textor, S. C., & Wilcox, C. S. (2001) · Annual Review of Medicine · doi:10.1146/annurev.med.52.1.421 · Cited by 164 · see citing works
A sympathetic view of the sympathetic nervous system and human blood pressure regulation
Joyner, M. J., Charkoudian, N., & Wallin, B. G. (2008) · Experimental Physiology · doi:10.1113/expphysiol.2007.039545 · Cited by 155 · see citing works
F2-isoprostanes as an indicator and risk factor for coronary heart disease
Davies, S. S., & Roberts, L. J. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.11.023 · Cited by 154 · see citing works
Endothelial Dysfunction and Salt-Sensitive Hypertension in Spontaneously Diabetic Goto-Kakizaki Rats
Cheng, Z. J., Vaskonen, T., Tikkanen, I. T., Nurminen, K., Ruskoaho, H. J., Vapaatalo, H., Müller, D., Park, J.-K., Luft, F. C., & Mervaala, E. M. A. (2001) · Hypertension · doi:10.1161/01.hyp.37.2.433 · Cited by 149 · see citing works
Renal Sympathetic Nerve Responses to Tempol in Spontaneously Hypertensive Rats
Shokoji, T., Nishiyama, A., Fujisawa, Y., Hitomi, H., Kiyomoto, H., Takahashi, N., Kimura, S., Kohno, M., & Abe, Y. (2003) · Hypertension · doi:10.1161/01.hyp.0000049621.85474.cf · Cited by 147 · see citing works
Characterization of an Animal Model of Postmenopausal Hypertension in Spontaneously Hypertensive Rats
Fortepiani, L. A., Zhang, H., Racusen, L. C., Roberts, L. J., & Reckelhoff, J. F. (2003) · Hypertension · doi:10.1161/01.hyp.0000046924.94886.ef · Cited by 147 · see citing works
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Systemic and Regional Hemodynamic Responses to Tempol in Angiotensin II–Infused Hypertensive Rats
Nishiyama, A., Fukui, T., Fujisawa, Y., Rahman, M., Tian, R., Kimura, S., & Abe, Y. (2001) · Hypertension · doi:10.1161/01.hyp.37.1.77 · Cited by 142 · see citing works
Endothelial dysfunction in human essential hypertension
Mordi, I. R., Mordi, N., Delles, C., & Tzemos, N. (2016) · Journal of Hypertension · doi:10.1097/hjh.0000000000000965 · Cited by 141 · see citing works
Participation of nitric oxide in different models of experimental hypertension
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Telomere Length and Oxidative Stress and Its Relation with Metabolic Syndrome Components in the Aging
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Antioxidants Block Angiotensin II-Induced Increases in Blood Pressure and Endothelin
Ortíz, M. C., Manriquez, M. C., Romero, J. C., & Juncos, L. A. (2001) · Hypertension · doi:10.1161/01.hyp.38.3.655 · Cited by 134 · see citing works
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Upregulation of Angiotensin-Converting Enzyme 2 by All- trans Retinoic Acid in Spontaneously Hypertensive Rats
Zhong, J., Huang, D., Yang, Y., Li, Y., Liu, G., Song, X., & Du, K. (2004) · Hypertension · doi:10.1161/01.hyp.0000146400.57221.74 · Cited by 129 · see citing works
Vitamin D, reactive oxygen species and calcium signalling in ageing and disease
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Genetic Demonstration of p47phox-Dependent Superoxide Anion Production in Murine Vascular Smooth Muscle Cells
Lavigne, M. C., Malech, H. L., Holland, S. M., & Leto, T. L. (2001) · Circulation · doi:10.1161/01.cir.104.1.79 · Cited by 126 · see citing works
Maternally Inherited Essential Hypertension Is Associated With the Novel 4263A>G Mutation in the Mitochondrial tRNA Ile Gene in a Large Han Chinese Family
Wang, S., Li, R., Fettermann, A., Li, Z., Qian, Y., Liu, Y., Wang, X., Zhou, A., Mo, J. Q., Yang, L., et al. (2011) · Circulation Research · doi:10.1161/circresaha.110.231811 · Cited by 127 · see citing works
Obesity and hypertension: mechanisms, cardio-renal consequences, and therapeutic approaches.
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Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats.
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Effect of high-salt diet on NO release and superoxide production in rat aorta
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The effects of exercise and training on human cardiovascular reflex control
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Association of mitochondrial SOD deficiency with salt-sensitive hypertension and accelerated renal senescence
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Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells
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AT1 receptor antagonist combats oxidative stress and restores nitric oxide signaling in the SHR
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Hyperbilirubinemia, Augmentation of Endothelial Function, and Decrease in Oxidative Stress in Gilbert Syndrome
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Role of Angiotensin II and Reactive Oxygen Species in Cyclosporine A–Dependent Hypertension
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Angiotensin II attenuates functional hyperemia in the mouse somatosensory cortex
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Superoxide: a key player in hypertension
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Candesartan Reduces Oxidative Stress and Inflammation in Patients with Essential Hypertension
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Erectile Dysfunction and Hypertension: Impact on Cardiovascular Risk and Treatment
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Inflammation and the metabolic syndrome: Role of angiotensin II and oxidative stress
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Oral administration of purple passion fruit peel extract attenuates blood pressure in female spontaneously hypertensive rats and humans
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The SOD Mimetic Tempol Ameliorates Glomerular Injury and Reduces Mitogen-Activated Protein Kinase Activity in Dahl Salt-Sensitive Rats
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Homocysteine and Essential Hypertension
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Tumor necrosis factor-α induces renal vasoconstriction as well as natriuresis in mice
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Vascular endothelial ageing, heartbeat after heartbeat
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Antenatal nicotine induces heightened oxidative stress and vascular dysfunction in rat offspring
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Estrogen or the AT1 Antagonist Olmesartan Reverses the Development of Profound Hypertension in the Congenic mRen2.Lewis Rat
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Hypertension and the Metabolic Syndrome
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An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension
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Antioxidants in Hypertension and Cardiovascular Disease
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Implications of Oxidative Stress and Homocysteine in the Pathophysiology of Essential Hypertension
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Nitric Oxide Mediates the Blood-Pressure Lowering Effect of Garlic in the Rat Two-Kidney, One-Clip Model of Hypertension
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Determinants of F2-isoprostane biosynthesis and inhibition in man
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Angiotensin-(1-7) modulates renin–angiotensin system associated with reducing oxidative stress and attenuating neuronal apoptosis in the brain of hypertensive rats
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Cellular mediators of renal vascular dysfunction in hypertension
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Coping with physiological oxidative stress: a review of antioxidant strategies in seals
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The molecular sources of reactive oxygen species in hypertension
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Sexual dimorphism in angiotensin II-induced hypertension and vascular alterations
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ROS During the Acute Phase of Ang II Hypertension Participates in Cardiovascular MAPK Activation But Not Vasoconstriction
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Superoxide Contributes to Development of Salt Sensitivity and Hypertension Induced by Nitric Oxide Deficiency
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Vascular biology of angiotensin and the impact of physical activity
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Central role of the AT1-receptor in atherosclerosis
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Ginkgo biloba extract (EGb 761) normalizes hypertension in 2K, 1C hypertensive rats: Role of antioxidant mechanisms, ACE inhibiting activity and improvement of endothelial dysfunction
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HYPERTENSION AND OXIDATIVE STRESS
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Physiological basis for a causal relationship of obstructive sleep apnoea to hypertension
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Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients
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The role of oxidative stress in angiotensin II hypertension
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Self-citation
Oxidative stress may explain how hypertension is maintained by normal levels of angiotensin II
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Self-citation
Subpressor Doses of Angiotensin II Increase Plasma F 2 -Isoprostanes in Rats
Reckelhoff, J. F., Zhang, H., Srivastava, K., Roberts, L. J., Morrow, J. D., & Romero, J. C. (2000) · Hypertension · doi:10.1161/01.hyp.35.1.476 · Cited by 88 · see citing works
Self-citation
Role of oxidative stress in angiotensin-induced hypertension
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Self-citation
Low-Dose Angiotensin II Increases Free Isoprostane Levels in Plasma
Haas, J. A., Krier, J. D., Bolterman, R. J., Juncos, L. A., & Romero, J. C. (1999) · Hypertension · doi:10.1161/01.hyp.34.4.983 · Cited by 81 · see citing works
Self-citation

Authors: Romero, J. C., & Reckelhoff, J. F.
Affiliations: Mayo Clinic (US)
ORCID: Romero, J. Carlos
Reckelhoff, Jane F.
Venue: Hypertension
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1999-10
Volume: 34
Issue: 4
Pages: 943-949
ISSN: 0194-911X (ISSN-L)
1524-4563
DOI: 10.1161/01.hyp.34.4.943
OpenAlex: W2075090912
Cited by: 358
References: 78
Citations by year: 2026: 3 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 10 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 8 · 2016: 19 · 2015: 9 · 2014: 6 · 2013: 9 · 2012: 19
FWCI: 2.87
Type: journal article
Language: en
Open access: closed
Locations: Hypertension (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association
National Institutes of Health
National Heart, Lung, and Blood Institute (HL 16496, HL‐51971, P01HL051971, R01HL016496)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords: angiotensin II, oxidative stress, essential hypertension, 8-isoprostane, superoxide, nitric oxide, peroxynitrite, endothelin, vasoconstriction, antinatriuretic effect, renovascular hypertension
MeSH terms: Angiotensin II, Animals, Humans, Hypertension, Nitric Oxide, Dinoprost, Oxidative Stress

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Role of Angiotensin and Oxidative Stress in Essential Hypertension

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