Sympathetic and haemodynamic responses to lipids in healthy human ageing

Plasma non-esterified fatty acids (NEFAs) activate the sympathetic nervous system and increase vascular resistance and blood pressure (BP); however, the response with ageing is not known. The objectives of this study were to characterize the cardiovascular, neural and endocrine responses to acute elevation of NEFA concentration. Seventeen healthy older volunteers (7 male and 10 female; age, 69 +/- 1 years; body mass index, 24 +/- 0 kg m(2); values are means +/- s.e.m.) received a 4 h intravenous infusion of the lipid emulsion Intralipid 20% or placebo (single-blind, randomized, balanced order) on two different days separated by at least 2 weeks. Muscle sympathetic nerve activity (MSNA), heart rate (HR), BP, cardiac output, leptin, insulin, aldosterone, angiotensin II and F(2)-isoprostanes were measured. The change in HR (+8.8 +/- 0.9 versus +3.0 +/- 0.9 beats min(1)), systolic BP (+13.9 +/- 2.2 versus +6.6 +/- 2.4 mmHg) and diastolic BP (+7.4 +/- 1.5 versus +1.3 +/- 0.8 mmHg) was significantly greater after Intralipid versus placebo infusions (P < 0.001). Lipid infusion increased MSNA burst frequency (+6.7 +/- 1.6 bursts min(1)), total MSNA (+45%; P < 0.001) and concentrations of insulin (+40%), aldosterone (+50%) and F(2)-isoprostanes (+80%), but not leptin. Hyperlipidaemia caused directionally opposite responses for insulin (increased) and calf vascular resistance (decreased) in men, whereas insulin and calf vascular resistance responses were severely blunted and non-existent, respectively, in women. We conclude that direct vascular mechanisms and central sympathetic activation contribute to the NEFA pressor response; though absolute values are higher, the change is not different compared with previous studies in a younger population.