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The Human Milk Oligosaccharide 3–Fucosyllactose Facilitates Preservation of Nitric Oxide‐Induced Vasodilation in Aortic Vessels In vitro
Author(s) -
Varadharaj Saradhadevi,
Helal Mustafa,
DuskaMcEwen Geralyn O,
Boslett Jim,
Pereira Suzette L,
Buck Rachael H,
Ahmed Naseeruddin,
Zweier Jay L
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb808
Subject(s) - vasodilation , nitric oxide , enos , medicine , endocrinology , endothelial dysfunction , sodium nitroprusside , phenylephrine , necrotizing enterocolitis , chemistry , nitric oxide synthase , blood pressure
Background The human milk oligosaccharides (HMOs) 2′‐Fucosyllactose (2′‐FL) and 3‐Fucosyllactose (3‐FL) structurally mimic human histo‐blood group antigens. It is estimated that ~1% of HMOs consumed are absorbed systemically. Although HMOs can reduce platelet‐neutrophil complex formation in vitro , direct effects on endothelial vascular reactivity and tone following an inflammatory stimulus are unknown. In vascular disease associated with intestinal ischemia, coronary ischemia, hypertension, diabetes and hyperlipidemia, vasodilation is impaired due to loss of endothelial nitric oxide synthase (eNOS) function with a pivotal switch from production of the vasodilator nitric oxide (NO) to vasoconstrictor superoxide (O 2 •− ). Necrotizing enterocolitis (NEC) is a risk factor in premature infants with congenital heart disease and pulmonary hypertension due to altered vascular reactivity. We hypothesize that HMO facilitates NO‐mediated vascular smooth muscle cell relaxation leading to increased vasodilation. Therefore, we investigated the effect of HMO‐3‐FL on NO‐dependent aortic vessel relaxation. Methods Studies were performed using rat thoracic aortic rings treated with or without 3‐FL and the vessel rings were grouped as Control, Lipopolysaccharide (LPS), LPS + 3‐FL. The rings were pre‐incubated with 3‐FL (250 μg/500 μl) followed by incubation with LPS for 4 hours in 5 μg/500 μl LPS/media. The rings were then assessed for endothelial‐dependent and independent relaxation by pre‐constricting vessels with phenylephrine (PHE) 1 μM and then progressive addition of acetylcholine (Ach) 0.001 to 100 uM or nitroprusside (SNP), 0.01 – 1000 nM. Vasorelaxation was calculated as a percentage of the PE‐induced maximal response. Results and Discussion Cumulative dosing of Ach or SNP to PHE‐pre‐constricted rings caused typical dose‐dependent relaxation in control aortic rings. However, after LPS treatment, this response was impaired with ~80% decrease. In rings that were pre‐incubated with 3‐FL, significant preservation of relaxation was seen with over 50% higher maximal relaxation compared to vehicle control LPS treatment. When pre‐incubated with 3‐FL (0.5mg/ml) the LPS stimulated aortic rings showed an increase in vasorelaxation (p<0.05) over the full dose range of NO donor (SNP). Thus, 3‐FL enhanced endothelial‐independent relaxation, which is based on the function of the smooth muscle in the vessel wall. These results suggest an approach to prevent or limit NEC by reversing vasoconstriction. Preservation of vasomotor activity and vasodilation by HMOs may provide a novel nutritional approach for the prevention of NEC‐associated vascular dysfunction.