Short-term high salt intake reduces brachial artery and microvascular function in the absence of changes in blood pressure.

OBJECTIVES: The aims of this study were to test the hypothesis that short-term high salt intake reduces macrovascular and microvascular endothelial function in the absence of changes in blood pressure and to determine whether acute exercise restores endothelial function after high salt in women. MATERIALS AND METHODS: Twelve women were administered high salt (11 g of sodium chloride for 7 days) and then underwent a weightlifting session. Brachial artery flow-mediated dilation and nitroglycerin dilation were measured with ultrasound at baseline, after high salt, and after weightlifting. Subcutaneous fat tissue biopsies were obtained at baseline, after high salt, and after weightlifting. Resistance arteries from biopsies were cannulated for vascular reactivity measurements in response to flow [flow-induced dilation (FID)] and acetylcholine. RESULTS: Blood pressure was similar before and after high salt diet. Brachial flow-mediated dilation was reduced after high salt diet but was not affected by acute weightlifting. Brachial nitroglycerin dilations were similar before and after high salt. FID and acetylcholine-induced dilation of resistance arteries were similar to that of before and after high salt diet. FID and acetylcholine-induced dilation was not altered by weightlifting after high salt diet. However, N-nitro-L-arginine methyl ester significantly reduced FID at baseline and after exercise but had no effect dilator reactivity after high salt diet alone. CONCLUSION: These data suggest that high salt intake reduces brachial artery endothelial function and switches the mediator of vasodilation in the microcirculation to a non-nitric oxide-dependent mechanism in healthy adults and acute exercise may switch the dilator mechanism back to nitric oxide during high salt diet.

The role of cyclo-oxygenase-1 in high-salt diet-induced microvascular dysfunction in humans.

KEY POINTS: Recent studies have shown that some of the deleterious effects of a high-salt (HS) diet are independent of elevated blood pressure and are associated with impaired endothelial function. Increased generation of cyclo-oxygenase (COX-1 and COX-2)-derived vasoconstrictor factors and endothelial activation may contribute to impaired vascular relaxation during HS loading. The present study aimed to assess the regulation of microvascular reactivity and to clarify the role of COX-1 and COX-2 in normotensive subjects on a short-term HS diet. The present study demonstrates the important role of COX-1 derived vasoconstrictor metabolites in regulation of microvascular blood flow during a HS diet. These results help to explain how even short-term HS diets may impact upon microvascular reactivity without changes in blood pressure and suggest that a vasoconstrictor metabolite of COX-1 could play a role in this impaired tissue blood flow. ABSTRACT: The present study aimed to assess the effect of a 1-week high-salt (HS) diet on the role of cyclo-oxygenases (COX-1 and COX-2) and the vasoconstrictor prostaglandins, thromboxane A2 (TXA2 ) and prostaglandin F2α (PGF2α ), on skin microcirculatory blood flow, as well as to detect its effect on markers of endothelial activation such as soluble cell adhesion molecules. Young women (n = 54) were assigned to either the HS diet group (N = 30) (∼14 g day(-1) NaCl ) or low-salt (LS) diet group (N = 24) (<2.3 g day(-1) NaCl ) for 7 days. Post-occlusive reactive hyperaemia (PORH) in the skin microcirculation was assessed by laser Doppler flowmetry. Plasma renin activity, plasma aldosterone, plasma and 24 h urine sodium and potassium, plasma concentrations of TXB2 (stable TXA2 metabolite) and PGF2α , soluble cell adhesion molecules and blood pressure were measured before and after the diet protocols. One HS diet group subset received 100 mg of indomethacin (non-selective COX-1 and COX-2 inhibitor), and another HS group subset received 200 mg of celecoxib (selective COX-2 inhibitor) before repeating laser Doppler flowmetry measurements. Blood pressure was unchanged after the HS diet, although it significantly reduced after the LS diet. Twenty-four hour urinary sodium was increased, and plasma renin activity and plasma aldosterone levels were decreased after the HS diet. The HS diet significantly impaired PORH and increased TXA2 but did not change PGF2α levels. Indomethacin restored microcirculatory blood flow and reduced TXA2 . By contrast, celecoxib decreased TXA2 levels but had no significant effects on blood flow. Restoration of of PORH by indomethacin during a HS diet suggests an important role of COX-1 derived vasoconstrictor metabolites in the regulation of microvascular blood flow during HS intake.

Adrenergic System Activation Mediates Changes in Cardiovascular and Psychomotoric Reactions in Young Individuals after Red Bull (©) Energy Drink Consumption.

Objectives. To assess the effect of Red Bull(©) on (1) blood glucose and catecholamine levels, (2) cardiovascular and respiratory function changes before, during, and after exercise, (3) reaction time, (4) cognitive functions, and (5) response to mental stress test and emotions in young healthy individuals (N=38). Methods. Heart rate (HR) and arterial blood pressure (ABP), blood glucose, adrenaline, and noradrenalin plasma levels were measured before and after Red Bull(©) intake. Participants were subjected to 4 different study protocols by randomized order, before and 30 minutes after consumption of 500 mL of Red Bull(©). Results. Mean ABP and HR were significantly increased at rest after Red Bull(©) intake. Blood glucose level and plasma catecholamine levels significantly increased after Red Bull(©) consumption. Heart rate, respiration rate, and respiratory flow rate were significantly increased during exercise after Red Bull(©) consumption compared to control condition. Intake of Red Bull(©) significantly improved reaction time, performance in immediate memory test, verbal fluency, and subject's attention as well as performance in mental stress test. Conclusion. This study demonstrated that Red Bull(©) has beneficial effect on some cognitive functions and effect on cardiovascular and respiratory system at rest and during exercise by increasing activity of the sympathetic nervous system.

Assessment of coronary hemodynamics and vascular function.

Coronary blood flow closely matches to metabolic demands of heart and myocardial oxygen consumption and is conditioned by function of coronary resistance vessels. The microvascular endothelium of coronary resistance vessels is exposed to a spatially and temporally regulated input from cardiomyocytes and the haemodynamic forces of the cardiac cycle. Functional measurements of coronary pressure and flow are important approaches that provide complementary information on the function of coronary vessel function that could not be assessed by the methods utilized for the anatomic characterization of coronary disease, such as coronary angiography. The goal of this paper is to review the methodologies for assessment of coronary vascular function and haemodynamics which are utilized in research and to discuss their potential applicability in the clinical settings.

Reduced flow-and acetylcholine-induced dilations in visceral compared to subcutaneous adipose arterioles in human morbid obesity.

BACKGROUND AND AIMS: The hypothesis of this study was that microvascular FID and AChID is impaired in visceral (VAT) compared to SAT arterioles in morbidly obese women. An Additional aim was to determine the mechanisms contributing to FID and AChID in VAT and SAT arterioles. METHODS AND RESULTS: Arterioles were obtained from SAT and VAT biopsies from women (BMI > 35 kg/m(2) ) undergoing bariatric surgery. Microvessels were cannulated for reactivity measurements in response to flow (pressure gradients of 10-100 cmH2 O) and to ACh (10(-9) -10(-4 ) M) with and without l-NAME, INDO, and PEG-catalase. NO and H2 O2 generation were detected in arterioles by fluorescence microscopy. FID and AChID of arterioles from VAT were reduced compared to SAT arterioles. In SAT arterioles, l-NAME, INDO, and PEG-catalase significantly reduced FID and AChID but had no effect individually on VAT arterioles' vasodilator reactivity. INDO +l-NAME reduced FID in VAT arterioles. NO-fluorescence was greater in arterioles from SAT compared to VAT arterioles. Vascular H2 O2 generation during flow was similar in both VAT and SAT. CONCLUSION: Our results suggest that VAT arterioles display reduced vasodilator reactivity to flow and ACh compared to SAT arterioles, mediated by different regulatory mechanisms in human obesity.

Basic cognitive functions across the menstrual cycle in a controlled female cohort.

AIM: To investigate the role of sex hormones in the modulation of specific cognitive functions across the menstrual cycle of young healthy women, and to apply improved study design by addressing limitations recognized in previous studies. METHODS: A homogenous group of 16 young healthy women, with no history of health problems related to menstrual cycle, major psychiatric and neurological disorders or addictions was included in study. All participants were medical students of similar age (21.56 ± 0.15 year). They were subjected to various cognitive tasks at three different phases of the menstrual cycle: early follicular phase, proven ovulatory phase and mid-luteal phase. Special concern was taken to validate blood hormone levels and to determine preovulatory luteinizing hormone (LH)-peak. RESULTS: Analysis of blood hormone levels confirmed that the test sessions were performed at appropriate time points. Most women were presented with the above average results on utilized cognitive tasks, with no significant changes in immediate memory, working memory, delayed recall, verbal learning, delayed verbal learning or verbal fluency in any phase of the menstrual cycle. In addition, test results did not correlate to measured hormone levels. CONCLUSIONS: The results suggest that changes in estrogen and progesterone levels during each menstrual cycle did not affect women's everyday functioning to any significant extent.

Effects of AT1 receptor blockade on plasma thromboxane A2 (TXA2) level and skin microcirculation in young healthy women on low salt diet.

OBJECTIVE: To determine the effect of AT1 receptor antagonism on skin microcirculation and plasma level of thromboxane A2 (TXA2). METHODS: Healthy women (n=20) maintained 7 days low salt (LS) diet (intake <40 mmol Na/day) without (LS) or together with 50 mg/per day of losartan (a selective AT1 receptor inhibitor) (LS diet+losartan group). Laser Doppler flowmetry (LDF) measurements of changes in post occlusive hyperemic blood flow, plasma concentration of stable TXA2 metabolite thromboxane B2 (TXB2) and plasma renin activity (PRA) aldosterone concentration, electrolytes (Na(+), K(+)), as well as blood pressure and heart rate were determined before and after study protocols. RESULTS: PRA and aldosterone increased significantly after 7 days of both LS diet and LS diet+losartan. LS diet or LS diet+losartan administrations had no significant effect on post-occlusion hyperemia While there was no change in TXB2 after LS diet TXB2 significantly increased after one week of LS+losartan compared to control levels (cTXB2 pg/mL control 101±80 vs. LS diet+losartan 190±116, p<0.05). CONCLUSION: These data suggest that inhibition of AT1 receptors could lead to activation of AT2 receptors, which maintain hyperemia, despite the increased level of vasoconstrictor TXA2. These findings also suggest an important role of crosstalk between renin-angiotensin system (RAS) and arachidonic acid metabolites in the regulation of microcirculation under physiological conditions.

Apolipoprotein E enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial NO synthase.

Apolipoprotein E (apoE) is widely expressed in mammalian tissues, and one of the important tissue-specific effects is the atheroprotection ascribed to macrophage-derived apoE in the arterial wall. However, underlying mechanisms are not well understood. In this study, using subcellular fractionation, confocal microscopy, and coimmunoprecipitation, we demonstrated that macrophage-derived apoE is internalized by endothelial cells and impacts the subcellular distribution/interaction of caveolin 1 (cav-1) and endothelial NO synthase (eNOS). The addition of apoE disrupts the heteromeric complex formed between cav-1 and eNOS, and increases NO production. Sterol and oxysterol enhance endothelial cav-1/eNOS interaction and suppress NO production, but these effects are reversed by apoE. Silencing endothelial cav-1 attenuates apoE-induced NO production, establishing the importance of the cav-1-eNOS interaction for the increment in endothelial NO produced by apoE. Consistent with these observations, macrophage-derived apoE significantly improves vasodilation to acetylcholine in resistance arteries isolated from adipose tissue of obese humans. We conclude that macrophage-derived apoE enhances endothelial NO production by disrupting the inhibitory interaction of eNOS with cav-1. These results establish a novel mechanism by which apoE modulates endothelial cell function.

Influence of short-term changes in sex hormones on serum concentrations of cellular adhesion molecules in young healthy women.

AIM: To determine if short-term changes in sex hormones (such as cyclic changes within the menstrual cycle) can influence the serum concentration of soluble cell adhesion molecules (CAMs). METHODS: Sixteen healthy young women with normal cycles participated in this study. Serum levels of sICAM-1, sVCAM-1 and E-selectin were determined in three different phases of the menstrual cycle: a) early follicular (EF) phase, b) ovulatory (O) phase and c) midluteal (ML) phase, by standardized ELISA-based kits. To confirm the exact assessment of menstrual cycle phases, serum levels of estrogen, progesterone, LH and FSH were measured. RESULTS: There were significant oscillations in serum female sex hormones concentration over the cycle duration, as expected the level of estrogen (E2) and progesterone (PROG) was the lowest in EF phase, the highest E2 appeared in O phase, and both E2 and PROG were present in high concentrations during ML phase. There was a significant positive correlation between E2 and serum soluble ICAM -1 concentrations (p=0,041, correlation coefficient 0,306). However, there was no significant change in other soluble CAMs concentration during the menstrual cycle. CONCLUSIONS: Results of our study suggest that short-term changes in female sex hormone levels could modulate expression of soluble ICAM-1, but not VCAM -1 or E-selectin in extent that would affect a young woman's health.

Effects of hyperbaric oxygenation on vascular reactivity to angiotensin II and angiotensin-(1-7) in rats.

OBJECTIVE: To assess and elucidate the mechanisms of hyperbaric oxygenation (HBO2) effects on vascular reactivity to angiotensin-(1-7) [ANG-(1-7)] and angiotensin II (ANG II). METHODS: Rat aortic rings (HBO2 vs. control group) were used to test responses to ANG II, ANG II+ ANG-(1-7) or ANG-(1-7) after noradrenaline precontraction in the presence/absence of MS-PPOH, a specific CYP 450-epoxygenase inhibitor, and glibenclamide, a KATP channels inhibitor. mRNA expression studies of specific CYP isozymes have been conducted as well. RESULTS: The mean contraction (expressed as percent of maximal contraction) for ANG II was similar between groups. Contraction for ANG II + ANG-(1-7) was 15% +/- 10 (HBO2) and 20% +/- 9 (control). There was a significant decrease between the contraction response to ANG II (HBO2) and the response to ANG II + ANG-(1-7) in the HBO2 group, without such a difference within the control group. Mean percentage of noradrenaline precontraction decrease after ANG-(1-7) addition was significantly different [10% +/- 9 (control) and 19% +/- 11 (HBO2)]. The epoxygenase inhibitor MS-PPOH in HBO2 animals reversed these changes. Glibenclamide had no effect on relaxation in response to ANG-(1-7). Expression of CYP4A2, CYP4A3 and CYP2J3 mRNA was not significantly altered with HBO, whereas CYP4A1 was significantly upregulated. CONCLUSIONS: Our results suggest a role for epoxyeicosatrienoic acids in modulating relaxation response to ANG-(1-7) with HBO2 that is conducted via potassium channels other than KATP channels. HBO2 increased the responses to ANG-(1-7) after precontraction with noradrenaline. The difference between the response to ANG II in the HBO2 group and ANG II + ANG-(1-7) in the HBO2 group (the contraction force of the peptide combination being lower), without such difference in the control group, suggests an influence ofHBO2 on vascular reactivity.