title: Attenuated flow-induced dilatation of middle cerebral arteries is related to increased vascular oxidative stress in rats on a short-term high salt diet.
abstract: Recent studies have shown that high salt (HS) intake leads to endothelial dysfunction and impaired vascular reactivity in different vascular beds in both animal and human models, due to increased oxidative stress. The objective of this study was to assess vascular response to flow-induced dilatation (FID) and to elucidate the role of vascular oxidative stress/antioxidative capacity in middle cerebral arteries (MCAs) of HS-fed rats in vitro. The novelty of this study is in demonstrating impaired flow-induced dilatation of MCAs and down-regulation of vascular antioxidant genes with HS intake, leading to increased levels of oxidative stress in blood vessels and peripheral lymph organs, which together contribute to impaired FID. In addition, results show increased oxidative stress in leukocytes of peripheral lymph organs, suggesting the occurrence of inflammatory processes due to HS intake. Recirculation of leukocytes might additionally increase vascular oxidative stress in vivo.
  
  
  
  The aim of this study was to determine flow-induced dilatation (FID) and the role of oxidative stress/antioxidative capacity in isolated, pressurized middle cerebral arteries (MCAs) of high salt (HS)-fed rats. Healthy male Sprague-Dawley rats (11 weeks old) were fed low salt (0.4% NaCl; LS group) or high salt (4% NaCl; HS group) diets for 1 week. Reactivity of MCAs in response to stepwise increases in pressure gradient (Δ10-Δ100 mmHg) was determined in the absence or presence of the superoxide dismutase (SOD) mimetic TEMPOL and/or the nitric oxide synthases (NOS) inhibitor N(ω) -nitro-l-arginine methyl ester (l-NAME). mRNA levels of antioxidative enzymes, NAPDH-oxidase components, inducible (iNOS) and endothelial nitric oxide synthases (eNOS) were determined by quantitative real-time PCR. Blood pressure (BP), antioxidant enzymes activity, oxidative stress in peripheral leukocytes, lipid peroxidation products and the antioxidant capacity of plasma were measured for both groups. FID was reduced in the HS group compared to the LS group. The presence of TEMPOL restored dilatation in the HS group, with no effect in the LS group. Expression of glutathione peroxidase 4 (GPx4) and iNOS in the HS group was significantly decreased; oxidative stress was significantly higher in the HS group compared to the LS group. HS intake significantly induced basal reactive oxygen species production in the leukocytes of mesenteric lymph nodes and splenocytes, and intracellular production after stimulation in peripheral lymph nodes. Antioxidant enzyme activity and BP were not affected by HS diet. Low GPx4 expression, increased superoxide production in leukocytes, and decreased iNOS expression are likely to underlie increased oxidative stress and reduced nitric oxide bioavailability, leading to impairment of FID in the HS group without changes in BP values.
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Cosic
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jukic
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Stupin
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Martina
authors.initials: M
authors.lastname: Mihalj
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Mihaljevic
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Novak
authors.affiliation: Department of Biology, J. J. Strossmayer University of Osijek, Croatia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Vukovic
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Ines
authors.initials: I
authors.lastname: Drenjancevic
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D004106:Dilatation; D004730:Endothelium, Vascular / Q000502:physiology; D005979:Glutathione Peroxidase / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D020768:Middle Cerebral Artery / Q000378:metabolism / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017673:Sodium Chloride, Dietary; D002374:Catalase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase