June 1, 2007Open Access
Acute elevation of plasma non-esterified fatty acids increases pulse wave velocity and induces peripheral vasodilation in humansin vivo
Key Result
Intralipid infusion to elevate plasma non-esterified fatty acids increased pulse wave velocity, systolic blood pressure, pulse pressure, and forearm blood flow compared with control (P<0.05).
Study Design
Type
RCT (n=9)
Randomization
Cross-over
Structured PICO
Does acute elevation of plasma non-esterified fatty acids using Intralipid infusion increase pulse wave velocity and induce peripheral vasodilation in healthy subjects?
P
Population
Healthy subjects (n=9 for main study, n=6 for positive control study)
I
Intervention
Intralipid infused for 2 hours to elevate plasma NEFAs, with caffeine (90 microg x min(-1) x dl(-1)) administered into the brachial artery during the last 15 minutes
C
Comparator
Glycerol administered as Control infusion
O
Outcome
Simultaneous assessment of blood pressure, pulse wave velocity, forearm blood flow, and sympathetic nervous system activitysurrogate
Acute elevation of plasma non-esterified fatty acids increases pulse wave velocity, systolic blood pressure, and forearm blood flow through mechanisms independent of adenosine receptor stimulation.
Main Result
p-value: p=<0.05
Abstract
Plasma NEFA (non-esterified fatty acid) concentrations are elevated in patients with obesity. In the present study we first aimed to provide an integral haemodynamic profile of elevated plasma NEFAs by the simultaneous assessment of blood pressure, pulse wave velocity, FBF (forearm blood flow) and sympathetic nervous system activity during acute elevation of NEFAs. Secondly, we hypothesized that NEFA-induced vasodilation is mediated by adenosine receptor stimulation. In a randomized cross-over trial in healthy subjects, Intralipid was infused for 2 h to elevate plasma NEFAs. Glycerol was administered as the Control infusion. We assessed blood pressure, pulse wave velocity, FBF (using venous occlusion plethysmography) and sympathetic nervous system activity by measurement of noradrenaline and adrenaline. During the last 15 min of Intralipid/Control infusion, the adenosine receptor antagonist caffeine (90 microg x min(-1) x dl(-1)) was administered into the brachial artery of the non-dominant arm. Compared with Control infusion, Intralipid increased pulse wave velocity, SBP (systolic blood pressure) and pulse pressure, as well as FBF (from 1.8+/-0.2 to 2.7+/-0.6 and from 2.3+/-0.2 to 2.7+/-0.6 ml x min(-1) x dl(-1) for Intralipid compared with 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 NEFA levels increased pulse wave velocity, SBP and pulse pressure. FBF was also increased, either by baroreflex-mediated inhibition of the sympathetic nervous system or by a direct vasodilating effect of NEFAs. As the adenosine receptor antagonist caffeine could not antagonize the vasodilator response, this response is not mediated by adenosine receptor stimulation.