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.

Acute elevation of triglycerides increases left ventricular contractility and alters ventricular-vascular interaction

“…While FFAs and triglycerides were measured at similar times, we did not undertake formal protocols to prevent lipolysis ex vivo, and this may have affected our results. The results from this study suggest that the acute effects of increased circulating triglycerides may have very different effects compared with the chronic setting, such as potential vasoconstriction and increased BP with longer exposure to raised lipids (26,29). However, this is only speculation, since the current study investigated the acute but not chronic response to IFE.…”

Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans

“…Most studies are in agreement that NEFAs promote insulin resistance and impair endothelium-dependent vasodilation [22][23][24]; however, the endothelial dysfunction documented in these investigations is typically associated with a paradoxical increase in basal limb blood flow. Although few studies have examined the underlying mechanisms of increased basal limb blood flow from elevated NEFA levels [25][26][27], possible explanations include insulin-induced NO release or vasodilating prostaglandin production [26].…”

Phosphorylation of GSK-3β Mediates Intralipid-induced Cardioprotection against Ischemia/Reperfusion Injury

“…The effect of Intralipid on vasculature is also controversial 37–39 . Intralipid has been shown to promote peripheral vasodilation in humans 37 .…”

“…Intralipid has been shown to promote peripheral vasodilation in humans 37 . Osanai et al, however showed that Intralipid impaired postischemic endothelium-dependent vasodilatation in the canine iliac artery 39 .…”