Acute elevation of plasma non-esterified fatty acids increases pulse wave velocity and induces peripheral vasodilation in humans in vivo

Niels P Riksen (1) , Marlies Bosselaar , Stephan Jl Bakker , Robert J Heine , Gerard A Rongen , Cees J Tack , Paul Smits

1 Pharmacology-Toxicology

Plasma free fatty acid (FFA) concentrations are elevated in patients with obesity. We aimed to provide an integral haemodynamic profile of elevated plasma FFA by the simultaneous assessment of blood pressure, pulse wave velocity, forearm blood flow (FBF), and sympathetic nervous system activity during acute elevation of FFA. Secondly, we hypothesized that FFA-induced vasodilation is mediated by adenosine receptor stimulation. In a randomized crossover trial in healthy subjects, Intralipid was infused for 2 hours to elevate plasma FFA. Glycerol was administered as Control infusion. We assessed blood pressure, pulse wave velocity, FBF (venous occlusion plethysmography), and sympathetic nervous system activity by measurements of noradrenaline and adrenaline. During the last 15 minutes of Intralipid/Control infusion, the adenosine receptor antagonist caffeine (90 microgram/min/dl) was administered into the brachial artery of the nondominant arm. Compared with Control infusion, Intralipid increased pulse wave velocity, systolic blood pressure and pulse pressure, as well as FBF (FBF increased from 1.8±0.2 to 2.7±0.6 and from 2.3±0.2 to 2.7±0.6 ml/min/dl for Intralipid versus Control infusion; P<0.05, n=9). Although in a positive control study caffeine attenuated adenosine-induced forearm vasodilation (P<0.01, n=6), caffeine had no effect on Intralipid-induced vasodilation (P=0.5). In conclusion, elevation of plasma FFA levels increases pulse wave velocity, systolic blood pressure, and pulse pressure. Also, FBF is increased, either by baroreflex-mediated inhibition of the sympathetic nervous system, or by a direct vasodilating effect of FFA. As the adenosine receptor antagonist caffeine could not antagonize the vasodilator response, it is not mediated by adenosine receptor stimulation.

Mots clés: Medicine

Niels P Riksen, Marlies Bosselaar, Stephan Jl Bakker, Robert J Heine, Gerard A Rongen, et al.. Acute elevation of plasma non-esterified fatty acids increases pulse wave velocity and induces peripheral vasodilation in humans in vivo. Clinical Science, 2007, 113 (1), pp.33-40. ⟨10.1042/CS20060365⟩. ⟨hal-00479360⟩