Post-prandial hyperlipidaemia results in systemic nitrosative stress and impaired cerebrovascular function in the aged

Christopher J Marley, Danielle Hodson, Julien V Brugniaux, Lewis Fall, Damian Miles Bailey

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Abstract

Post-prandial hyperlipidaemia (PPH) acutely impairs systemic vascular endothelial function, potentially attributable to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability (oxidative-nitrosative stress). However, it remains to be determined whether this extends to the cerebrovasculature. To examine this, 38 (19 young (≤ 35 years) and 19 aged (≥ 60 years)) healthy males were recruited. Cerebrovascular function (middle cerebral artery velocity, MCAv) and cerebrovascular reactivity to hypercapnea (CVRCO2Hyper) and hypocapnea (CVRCO2Hypo) were determined via trans-cranial Doppler ultrasound and capnography. Venous blood samples were obtained for the assessment of triglycerides (photometry), glucose (photometry), insulin (radio-immunoassay), ascorbate free radical (A•−, electron paramagnetic resonance spectroscopy) and nitrite (NO2-, ozone-based chemiluminescence) in the fasted state prior to and 4 hours following consumption of a standardised high-fat meal (1,362 kcal; 130g of fat). Circulating triglycerides, glucose and insulin increased in both groups following the high-fat meal ( P < 0.05), with triglycerides increasing by 1.37 + 1.09 mmol/L in the young and 1.54 + 1.00 mmol/L in the aged ( P < 0.05). This resulted in an increased systemic formation of free radicals in the young ( P < 0.05) but not the aged ( P > 0.05) and corresponding reduction in NO2- in both groups ( P < 0.05). While the meal had no effect on MCAv in either age group, CVRCO2Hyper was selectively impaired in the aged ( P < 0.05). These findings indicate that PPH causes acute cerebrovascular dysfunction in the aged subsequent to systemic nitrosative stress.
Original languageEnglish
Article numberCS20171406
Pages (from-to)2807-2812
JournalClinical Science
Volume131
Issue number32
Early online date20 Oct 2017
DOIs
Publication statusPublished - 28 Nov 2017

Keywords

  • Aging
  • Cerebrovascular Function
  • High-fat meal
  • Hyperlipidaemia
  • oxidative stress
  • Oxidative-Nitrosative stress

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