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.

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 (H2O2) 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.

The effects of consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) enriched hen eggs on endothelium-dependent and endothelium-independent vasodilation in microcirculation, and on endothelial activation and inflammation were determined in young healthy individuals. Control group (N = 21) ate three regular hen eggs/daily (249 mg n-3 PUFAs/day), and n-3 PUFAs group (N = 19) ate three n-3 PUFAs enriched hen eggs/daily (1053 g n-3 PUFAs/day) for 3 weeks. Skin microvascular blood flow in response to iontophoresis of acetylcholine (AChID; endothelium-dependent) and sodium nitroprusside (SNPID; endothelium-independent) was assessed by laser Doppler flowmetry. Blood pressure (BP), body composition, body fluid status, serum lipid and free fatty acids profile, and inflammatory and endothelial activation markers were measured before and after respective dietary protocol. Results: Serum n-3 PUFAs concentration significantly increased, AChID significantly improved, and SNPID remained unchanged in n-3 PUFAs group, while none was changed in Control group. Interferon-γ (pro-inflammatory) significantly decreased and interleukin-10 (anti-inflammatory) significantly increased in n-3 PUFAs. BP, fat free mass, and total body water significantly decreased, while fat mass, interleukin-17A (pro-inflammatory), interleukin-10 and vascular endothelial growth factor A significantly increased in the Control group. Other measured parameters remained unchanged in both groups. Favorable anti-inflammatory properties of n-3 PUFAs consumption potentially contribute to the improvement of microvascular endothelium-dependent vasodilation in healthy individuals.

The goal of the present study was to examine the effect of 1 wk of high salt (HS) intake and the role of oxidative stress in changing the mechanisms of flow-induced dilation (FID) in isolated pressurized middle cerebral arteries of male Sprague-Dawley rats ( n = 15-16 rats/group). Reduced FID in the HS group was restored by intake of the superoxide scavenger tempol (HS + tempol in vivo group). The nitric oxide (NO) synthase inhibitor N-nitro-l-arginine methyl ester, cyclooxygenase inhibitor indomethacin, and selective inhibitor of microsomal cytochrome P-450 epoxidase activity N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide significantly reduced FID in the low salt diet-fed group, whereas FID in the HS group was mediated by NO only. Cyclooxygenase-2 mRNA (but not protein) expression was decreased in the HS and HS + tempol in vivo groups. Hypoxia-inducible factor-1α and VEGF protein levels were increased in the HS group but decreased in the HS + tempol in vivo group. Assessment by direct fluorescence of middle cerebral arteries under flow revealed significantly reduced vascular NO levels and increased superoxide/reactive oxygen species levels in the HS group. These results suggest that HS intake impairs FID and changes FID mechanisms to entirely NO dependent, in contrast to the low-salt diet-fed group, where FID is NO, prostanoid, and epoxyeicosatrienoic acid dependent. These changes were accompanied by increased lipid peroxidation products in the plasma of HS diet-fed rats, increased vascular superoxide/reactive oxygen species levels, and decreased NO levels, together with increased expression of hypoxia-inducible factor-1α and VEGF. NEW & NOTEWORTHY High-salt (HS) diet changes the mechanisms of flow-induced dilation in rat middle cerebral arteries from a combination of nitric oxide-, prostanoid-, and epoxyeicosatrienoic acid-dependent mechanisms to, albeit reduced, a solely nitric oxide-dependent dilation. In vivo reactive oxygen species scavenging restores flow-induced dilation in HS diet-fed rats and ameliorates HS-induced increases in the transcription factor hypoxia-inducible factor-1α and expression of its downstream target genes.

The present study was aimed at assessing endothelium-dependent vasorelaxation, at measuring superoxide production in the aorta and femoral artery, and at determining antioxidative enzyme expression and activity in aortas of male Sprague-Dawley rats (N = 135), randomized to an A-HBO2 group exposed to a single hyperbaric oxygenation session (120′ of 100% O2 at 2.0 bars), a 24H-HBO2 group (single session, examined 24 h after exposure), a 4D-HBO2 group (4 consecutive days of single sessions), and a CTRL group (untreated group). Vasorelaxation of aortic rings in response to acetylcholine (AChIR) and to reduced pO2 (HIR) was tested in vitro in the absence/presence of NOS inhibitor L-NAME and superoxide scavenger TEMPOL. eNOS, iNOS, antioxidative enzyme, and NADPH oxidase mRNA expression was assessed by qPCR. Serum oxidative stress markers and enzyme activity were assessed by spectrometry, and superoxide production was determined by DHE fluorescence. Impaired AChIR and HIR in the A-HBO2 group were restored by TEMPOL. L-NAME inhibited AChIR in all groups. Serum oxidative stress and superoxide production were increased in the A-HBO2 group compared to all other groups. The mRNA expression of iNOS was decreased in the A-HBO2 and 24H-HBO2 groups while SOD1 and 3 and NADPH oxidase were increased in the 4D-HBO2 group. The expression and activity of catalase and glutathione peroxidase were increased in the 4D-HBO2 group as well. AChIR was NO dependent. Acute HBO2 transiently impaired vasorelaxation due to increased oxidative stress. Vasorelaxation was restored and oxidative stress was normalized 24 h after the treatment.

Carnosine is a dipeptide synthesized in the body from β-alanine and L-histidine. It is found in high concentrations in the brain, muscle, and gastrointestinal tissues of humans and is present in all vertebrates. Carnosine has a number of beneficial antioxidant properties. For example, carnosine scavenges reactive oxygen species (ROS) as well as alpha-beta unsaturated aldehydes created by peroxidation of fatty acid cell membranes during oxidative stress. Carnosine can oppose glycation, and it can chelate divalent metal ions. Carnosine alleviates diabetic nephropathy by protecting podocyte and mesangial cells, and can slow down aging. Its component, the amino acid beta-alanine, is particularly interesting as a dietary supplement for athletes because it increases muscle carnosine, and improves effectiveness of exercise and stimulation and contraction in muscles. Carnosine is widely used among athletes in the form of supplements, but rarely in the population of cardiovascular or diabetic patients. Much less is known, if any, about its potential use in enriched food. In the present review, we aimed to provide recent knowledge on carnosine properties and distribution, its metabolism (synthesis and degradation), and analytical methods for carnosine determination, since one of the difficulties is the measurement of carnosine concentration in human samples. Furthermore, the potential mechanisms of carnosine’s biological effects in musculature, metabolism and on immunomodulation are discussed. Finally, this review provides a section on carnosine supplementation in the form of functional food and potential health benefits and up to the present, neglected clinical use of carnosine.

Physical activity has a beneficial effect on systemic hemodynamics, physical strength, and cardiac function in cardiovascular (CV) patients. Potential beneficial effects of dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs), such as α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid on hemorheology, vascular function, inflammation and potential to improve physical performance as well as other CV parameters are currently investigated. Recent meta-analysis suggests no effect of n-3 PUFA supplementation on CV function and outcomes of CV diseases. On the other hand, some studies support beneficial effects of n-3 PUFAs dietary intake on CV and muscular system, as well as on immune responses in healthy and in CV patients. Furthermore, the interaction of exercise and dietary n-3 PUFA intake is understudied. Supplementation of n-3 PUFAs has been shown to have antithrombotic effects (by decreasing blood viscosity, decreasing coagulation factor and PAI-1 levels and platelet aggregation/reactivity, enhancing fibrinolysis, but without effects on erythrocyte deformability). They decrease inflammation by decreasing IL-6, MCP-1, TNFα and hsCRP levels, expression of endothelial cell adhesion molecules and significantly affect blood composition of fatty acids. Treatment with n-3 PUFAs enhances brachial artery blood flow and conductance during exercise and enhances microvascular post-occlusive hyperemic response in healthy humans, however, the effects are unknown in cardiovascular patients. Supplementation of n-3 PUFAs may improve anaerobic endurance and may modulate oxygen consumption during intense exercise, may increase metabolic capacity, enhance endurance capacity delaying the onset of fatigue, and improving muscle hypertrophy and neuromuscular function in humans and animal models. In addition, n-3 PUFAs have anti-inflammatory and anti-nociceptive effects and may attenuate delayed-onset muscle soreness and muscle stiffness, and preserve joint mobility. On the other hand, effects of n-3 PUFAs were variably observed in men and women and they vary depending on dietary protocol, type of supplementation and type of sports activity undertaken, both in healthy and cardiovascular patients. In this review we will discuss the physiological effects of n-3 PUFA intake and exercise on hemorheology, microvascular function, immunomodulation and inflammation and physical performance in healthy persons and in cardiovascular diseases; elucidating if there is an interaction of exercise and diet.

Previously, a facilitating effect of hyperbaric oxygenation (HBO₂) on aortic ring responses to angiotensin-(1-7) in healthy rats was reported, with epoxyeicosatrienoic acids (EETs) possibly playing an important role. The aim of this study was to assess whether HBO₂ exerts similar effects in diabetic rats and to further explore the role of specific cytochrome P450 (CYP) enzymes in changes induced by HBO₂. Aortic relaxation to angiotensin-(1-7) was significantly higher in HBO₂ diabetic rats compared to control diabetic rats, while HBO₂ had no effect on angiotensin II contraction. N-methylsulphonyl-6-(2-propargyloxyphenyl/hexanamide inhibited the facilitation of angiotensin-(1-7) responses in HBO₂ rats, suggesting an important role of EETs in this modulation. mRNA expression of CYP2J3 and protein expression of CYP2C11 were significantly upregulated in HBO₂ diabetic rats, whereas CYP4A1, CYP4A2 and CYP4A3 mRNA and CYP2J3 protein expression was similar between groups. Mean arterial pressure, ferric reducing ability of plasma and Thiobarbituric Acid Reactive Substances levels and serum angiotensin-(1-7) concentrations were not significantly changed.