title: Acute elevation of plasma non-esterified fatty acids increases pulse wave velocity and induces peripheral vasodilation in humans in vivo.
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.
authors.affiliation: Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. N.Riksen@aig.umcn.nl
authors.forename: Niels P
authors.initials: NP
authors.lastname: Riksen
authors.forename: Marlies
authors.initials: M
authors.lastname: Bosselaar
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heine
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Rongen
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Tack
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D001341:Autonomic Nervous System; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000493:pharmacokinetics; D003187:Compliance; D018592:Cross-Over Studies; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007328:Insulin / Q000097:blood; D011674:Pulse; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D005217:Fat Emulsions, Intravenous; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D002110:Caffeine; D000241:Adenosine