Seven-Day Salt Loading Impairs Microvascular Endothelium-Dependent Vasodilation without Changes in Blood Pressure, Body Composition and Fluid Status in Healthy Young Humans.

OBJECTIVES: We aimed to assess whether a 7-day high-salt (HS) diet affects endothelium-dependent and/or endothelium-independent microvascular function in the absence of changes in arterial blood pressure (BP), and to determine whether such microvascular changes are associated with changes in body composition and fluid status in healthy young humans. MATERIALS AND METHODS: Fifty-three young healthy individuals (28 women and 25 men) were assigned to a 7-day low-salt diet (<3.5 g salt/day) followed by a 7-day HS diet (∼14 g salt/day). Skin microvascular blood flow in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) was assessed by laser Doppler flowmetry, and BP, heart rate (HR), plasma renin activity (PRA), serum aldosterone, serum and 24 h-urine sodium, potassium, urea and creatinine levels, together with body composition and fluid status measurement with a 4-terminal portable impedance analyzer were measured before and after diet protocols. RESULTS: BP, HR, body composition and fluid status were unchanged, and PRA and serum aldosterone level were significantly suppressed after HS diet. ACh-induced dilation (AChID) was significantly impaired, while SNP-induced dilation was not affected by HS diet. Impaired AChID and increased salt intake, as well as impaired AChID and suppressed renin-angiotensin system were significantly positively correlated. Changes in body composition and fluid status parameters were not associated with impaired AChID. CONCLUSION: 7-day HS diet impairs microvascular reactivity by affecting its endothelium-dependent vasodilation in young healthy individuals. Changes are independent of BP, body composition changes or fluid retention, but are the consequences of the unique effect of HS on endothelial function.

Short-Term High-NaCl Dietary Intake Changes Leukocyte Expression of VLA-4, LFA-1, and Mac-1 Integrins in Both Healthy Humans and Sprague-Dawley Rats: A Comparative Study.

This study is aimed at assessing the effects of a short-term high-salt (HS) diet on the peripheral blood leukocyte (PBL) activation status in healthy rats and young human individuals. Distribution of PBL subpopulations and surface expression of integrins were determined using flow cytometry in 36 men and women on a 7-day low-salt diet (<3.2 g salt/day) immediately followed by a 7-day HS diet (~14 g salt/day) or in Sprague-Dawley (SD) rats (n = 24) on a 0.4% NaCl diet (aLS group) or a 4% NaCl diet (aHS group) for 7 days. The aHS group presented with an increased frequency of granulocytes, while the frequency of lymphocytes was reduced. Although in humans HS diet reduced the expression of CD11b(act) integrin on lymphocytes, the frequency of CD11b(act)-bearing cells among all PBL subsets was increased. The aHS group of rats exhibited increased expression of total CD11b/c in granulocytes and CD3 lymphocytes. The expression of CD11a was significantly reduced in all PBL subsets from human subjects and increased in the aHS group. CD49d expression on all PBL subsets was significantly decreased in both humans and rats. In human subjects, we found reduced frequencies of intermediate monocytes accompanied by a reciprocal increase in classical monocytes. Present results suggest that a short-term HS diet can alter leukocytes' activation status and promote vascular low-grade inflammation.

High salt intake shifts the mechanisms of flow-induced dilation in the middle cerebral arteries of Sprague-Dawley rats.

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 Nω-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.

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

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.

Sex-related differences in forearm skin microvascular reactivity of young healthy subjects.

OBJECTIVE: To assess sex-related differences in forearm skin microvascular reactivity to vascular occlusion and cardiovascular health in young healthy women and men. METHODS: 203 young healthy individuals (67 men/136 women) participated in this study. Post-occlusive reactive hyperemia (PORH) in skin microcirculation following 1', 2' and 3' vascular occlusion period was assessed using laser Doppler flowmetry. Anthropometric parameters, body composition, blood pressure, heart rate and biochemical parameters were measured in all participants. Correlations between PORH and measured parameters were determined by using corresponding tests. RESULTS: Women had significantly higher forearm PORH following 1', 2' and 3' vascular occlusion than men. Women had lower body mass index and waist-to-hip ratio, but higher fat mass than men. Men had significantly higher blood pressure and lower heart rate than women. Also, women had lower hemoglobin, urea, creatinine and serum uric acid, but higher HDL cholesterol level than men. PORH was negatively associated with waist-to-hip ratio and systolic blood pressure only in women. CONCLUSIONS: Young healthy women exhibit higher skin microvascular reactivity to vascular occlusion compared to age-matched men. Increased systolic blood pressure or central obesity (waist-to-hip ratio) may pose greater risk to young healthy women than men by adversely affecting peripheral microvascular function.