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      Genetic Polymorphisms Associated with Reactive Oxygen Species and Blood Pressure Regulation

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          Abstract

          Hypertension is the most prevalent cause of cardiovascular disease and kidney failure but only about 50% of patients achieve adequate blood pressure control, in part, due to inter-individual genetic variations in the response to antihypertensive medication. Significant strides have been made toward the understanding of the role of reactive oxygen species (ROS) in the regulation of the cardiovascular system. However, the role of ROS in human hypertension is still unclear. Polymorphisms of some genes involved in the regulation of ROS production are associated with hypertension, suggesting their potential influence on blood pressure control and response to antihypertensive medication. This review provides an update on the genes associated with the regulation of ROS production in hypertension and discusses the controversies on the use of antioxidants in the treatment of hypertension, including the antioxidant effects of antihypertensive drugs.

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          H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase.

          Guangdong Yang, Lingyun Wu, Bo Jiang … (2008)
          Studies of nitric oxide over the past two decades have highlighted the fundamental importance of gaseous signaling molecules in biology and medicine. The physiological role of other gases such as carbon monoxide and hydrogen sulfide (H2S) is now receiving increasing attention. Here we show that H2S is physiologically generated by cystathionine gamma-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces H2S levels in the serum, heart, aorta, and other tissues. Mutant mice lacking CSE display pronounced hypertension and diminished endothelium-dependent vasorelaxation. CSE is physiologically activated by calcium-calmodulin, which is a mechanism for H2S formation in response to vascular activation. These findings provide direct evidence that H2S is a physiologic vasodilator and regulator of blood pressure.
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            Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling

            Ying Wang, Robyn Branicky, Alycia Noë … (2018)
            Wang et al. review the dual role of superoxide dismutases in controlling reactive oxygen species (ROS) damage and regulating ROS signaling across model systems as well as their involvement in human diseases.
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              Hypertension

              Suzanne Oparil, Paul K. Whelton, Anthony Rodgers … (2018)
              Systemic arterial hypertension is the most important modifiable risk factor for all-cause morbidity and mortality worldwide and is associated with an increased risk of cardiovascular disease (CVD). Fewer than half of those with hypertension are aware of their condition, and many others are aware but not treated or inadequately treated, although successful treatment of hypertension reduces the global burden of disease and mortality. The aetiology of hypertension involves the complex interplay of environmental and pathophysiological factors that affect multiple systems, as well as genetic predisposition. The evaluation of patients with hypertension includes accurate standardized blood pressure (BP) measurement, assessment of the patients' predicted risk of atherosclerotic CVD and evidence of target-organ damage, and detection of secondary causes of hypertension and presence of comorbidities (such as CVD and kidney disease). Lifestyle changes, including dietary modifications and increased physical activity, are effective in lowering BP and preventing hypertension and its CVD sequelae. Pharmacological therapy is very effective in lowering BP and in preventing CVD outcomes in most patients; first-line antihypertensive medications include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, dihydropyridine calcium-channel blockers and thiazide diuretics.
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 101083949
                Journal ID (pubmed-jr-id): 22416
                Journal ID (nlm-ta): Pharmacogenomics J
                Journal ID (iso-abbrev): Pharmacogenomics J.
                Title: The pharmacogenomics journal
                ISSN (Print): 1470-269X
                ISSN (Electronic): 1473-1150
                Publication date Nihms-submitted: 31 January 2019
                Publication date (Electronic): 06 February 2019
                Publication date (Print): August 2019
                Publication date PMC-release: 06 August 2019
                Volume: 19
                Issue: 4
                Pages: 315-336
                Affiliations
                [1. ]Research Center for Genetic Medicine, Children’s National Health System, 111 Michigan Ave, NW Washington DC 20010
                [2. ]Department of Medicine, Division of Renal Diseases & Hypertension, The George Washington University School of Medicine and Health Sciences, Walter G. Ross Hall, Suite 738, 2300 I Street, N.W. Washington, DC 20052
                Author notes
                Corresponding author: Santiago Cuevas, PhD, Staff Scientist II, Research Center for Genetic Medicine, Children’s National Health System, 111 Michigan Ave, NW, Washington DC 20010, Phone: 202 476 6156, Fax: 202 476 5650, scuevas@ 123456childrensnational.org
                Article
                Manuscript ID: NIHMS1517349
                DOI: 10.1038/s41397-019-0082-4
                PMC ID: 6650341
                PubMed ID: 30723314
                SO-VID: e9720691-4266-400c-9a4e-e4380b45ab4b
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                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

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                Subject: Article

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: hypertension,oxidative stress,reactive oxygen species,pharmacogenomics,antioxidant treatment
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: hypertension, oxidative stress, reactive oxygen species, pharmacogenomics, antioxidant treatment

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