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      Enhanced Antioxidative Defense by Vitamins C and E Consumption Prevents 7-Day High-Salt Diet-Induced Microvascular Endothelial Function Impairment in Young Healthy Individuals

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          Abstract

          This study aimed to examine whether the oral supplementation of vitamins C and E during a seven-day high salt diet (HS; ~14 g salt/day) prevents microvascular endothelial function impairment and changes oxidative status caused by HS diet in 51 (26 women and 25 men) young healthy individuals. Laser Doppler flowmetry measurements demonstrated that skin post-occlusive reactive hyperemia (PORH), and acetylcholine-induced dilation (AChID) were significantly impaired in the HS group, but not in HS+C+E group, while sodium nitroprusside-induced dilation remained unaffected by treatments. Serum oxidative stress markers: Thiobarbituric acid reactive substances (TBARS), 8-iso prostaglandin-F2α, and leukocytes’ intracellular hydrogen peroxide (H 2O 2) production were significantly increased, while ferric-reducing ability of plasma (FRAP) and catalase concentrations were decreased in the HS group. All these parameters remained unaffected by vitamins supplementation. Matrix metalloproteinase 9, antioxidant enzymes Cu/Zn SOD and glutathione peroxidase 1, and leukocytes’ intracellular superoxide production remained unchanged after the protocols in both HS and HS+C+E groups. Importantly, multiple regression analysis revealed that FRAP was the most powerful predictor of AChID, while PORH was strongly predicted by both FRAP and renin-angiotensin system activity. Hereby, we demonstrated that oxidative dis-balance has the pivotal role in HS diet-induced impairment of endothelial and microvascular function in healthy individuals which could be prevented by antioxidative vitamins consumption.

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          Most cited references38

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          Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial.

          Basic research and observational studies suggest vitamin E or vitamin C may reduce the risk of cardiovascular disease. However, few long-term trials have evaluated men at initially low risk of cardiovascular disease, and no previous trial in men has examined vitamin C alone in the prevention of cardiovascular disease. To evaluate whether long-term vitamin E or vitamin C supplementation decreases the risk of major cardiovascular events among men. The Physicians' Health Study II was a randomized, double-blind, placebo-controlled factorial trial of vitamin E and vitamin C that began in 1997 and continued until its scheduled completion on August 31, 2007. There were 14,641 US male physicians enrolled, who were initially aged 50 years or older, including 754 men (5.1%) with prevalent cardiovascular disease at randomization. Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. A composite end point of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular disease death). During a mean follow-up of 8 years, there were 1245 confirmed major cardiovascular events. Compared with placebo, vitamin E had no effect on the incidence of major cardiovascular events (both active and placebo vitamin E groups, 10.9 events per 1000 person-years; hazard ratio [HR], 1.01 [95% confidence interval {CI}, 0.90-1.13]; P = .86), as well as total myocardial infarction (HR, 0.90 [95% CI, 0.75-1.07]; P = .22), total stroke (HR, 1.07 [95% CI, 0.89-1.29]; P = .45), and cardiovascular mortality (HR, 1.07 [95% CI, 0.90-1.28]; P = .43). There also was no significant effect of vitamin C on major cardiovascular events (active and placebo vitamin E groups, 10.8 and 10.9 events per 1000 person-years, respectively; HR, 0.99 [95% CI, 0.89-1.11]; P = .91), as well as total myocardial infarction (HR, 1.04 [95% CI, 0.87-1.24]; P = .65), total stroke (HR, 0.89 [95% CI, 0.74-1.07]; P = .21), and cardiovascular mortality (HR, 1.02 [95% CI, 0.85-1.21]; P = .86). Neither vitamin E (HR, 1.07 [95% CI, 0.97-1.18]; P = .15) nor vitamin C (HR, 1.07 [95% CI, 0.97-1.18]; P = .16) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke (HR, 1.74 [95% CI, 1.04-2.91]; P = .04). In this large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men. clinicaltrials.gov Identifier: NCT00270647.
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            Role of vitamin C in the function of the vascular endothelium.

            Vitamin C, or ascorbic acid, has long been known to participate in several important functions in the vascular bed in support of endothelial cells. These functions include increasing the synthesis and deposition of type IV collagen in the basement membrane, stimulating endothelial proliferation, inhibiting apoptosis, scavenging radical species, and sparing endothelial cell-derived nitric oxide to help modulate blood flow. Although ascorbate may not be able to reverse inflammatory vascular diseases such as atherosclerosis, it may well play a role in preventing the endothelial dysfunction that is the earliest sign of many such diseases. Beyond simply preventing scurvy, evidence is mounting that ascorbate is required for optimal function of many dioxygenase enzymes in addition to those involved in collagen synthesis. Several of these enzymes regulate the transcription of proteins involved in endothelial function, proliferation, and survival, including hypoxia-inducible factor-1α and histone and DNA demethylases. More recently, ascorbate has been found to acutely tighten the endothelial permeability barrier and, thus, may modulate access of ascorbate and other molecules into tissues and organs. The issue of the optimal cellular content of ascorbate remains unresolved, but it appears that low millimolar ascorbate concentrations are normal in most animal tissues, in human leukocytes, and probably in the endothelium. Although there may be little benefit of increasing near maximal cellular ascorbate concentrations in normal people, many diseases and conditions have either systemic or localized cellular ascorbate deficiency as a cause for endothelial dysfunction, including early atherosclerosis, sepsis, smoking, and diabetes. A key focus for future studies of ascorbate and the vascular endothelium will likely be to determine the mechanisms and clinical relevance of ascorbate effects on endothelial function, permeability, and survival in diseases that cause endothelial dysfunction.
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              The human cutaneous circulation as a model of generalized microvascular function.

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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                20 March 2020
                March 2020
                : 9
                : 3
                : 843
                Affiliations
                [1 ]Department of Physiology and Immunology, Faculty of Medicine Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, Hr-31000 Osijek, Croatia; rasiclid@ 123456gmail.com (L.B.); ines.drenjancevic@ 123456mefos.hr (I.D.); martina.mihalj@ 123456gmail.com (M.M.); anita.matic@ 123456mefos.hr (A.M.); marko.stupin@ 123456gmail.com (M.S.); lukakolar.vu@ 123456gmail.com (L.K.); zrinka.mihaljevic@ 123456mefos.hr (Z.M.)
                [2 ]Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, Hr-31000 Osijek, Croatia
                [3 ]Department of Dermatology and Venereology, Osijek University Hospital, J. Huttlera 4, HR-31000 Osijek, Croatia
                [4 ]Department for Cardiovascular Disease, Osijek University Hospital, J. Huttlera 4, HR-31000 Osijek, Croatia
                [5 ]Department of Physiology and Immunology, Medical Faculty University of Rijeka, Ul. Braće Branchetta 20/1, HR-51000 Rijeka, Croatia; ines.mrakovcic.sutic@ 123456medri.uniri.hr
                [6 ]Department of Clinical Laboratory Diagnostics, Osijek University Hospital, J. Huttlera 4, HR-31000 Osijek, Croatia; seric.vatroslav@ 123456kbo.hr
                [7 ]Department of Pathophysiology, Physiology and Immunology, Faculty of Dental Medicine and Health Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 10E, HR-31000 Osijek, Croatia
                Author notes
                [* ]Correspondence: ana.stupin@ 123456mefos.hr ; Tel.: +385-31-512-800
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-0761-047X
                https://orcid.org/0000-0002-5734-5849
                https://orcid.org/0000-0001-7296-1669
                https://orcid.org/0000-0001-9617-0271
                https://orcid.org/0000-0002-6631-071X
                https://orcid.org/0000-0002-7446-0021
                Article
                jcm-09-00843
                10.3390/jcm9030843
                7141509
                32244956
                77812d56-4a20-4856-b2a0-71f54ee59026
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 February 2020
                : 18 March 2020
                Categories
                Article

                high-salt diet,microcirculation,endothelium,oxidative stress,antioxidative defense,vitamin c,vitamin e,renin-angiotensin system

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