Ascorbic Acid Improves Postischemic Vasodilatation Impaired by Infusion of Soybean Oil into Canine Iliac Artery

Abstract

This study was conducted to (a) assess postischemic vasodilatation by changes in the vascular cross-sectional area using simultaneous intravascular two-dimensional and Doppler ultrasound before and after the infusion of Intralipid (Pharmacia & Upjohn, Peapack, NJ, U.S.A.); (b) evaluate how antioxidant ascorbic acid modifies the effects of Intralipid on postischemic vasodilatation: and (c) clarify the changes in plasma nitrite and nitrate (NOx-) levels after the infusion of Intralipid with and without ascorbic acid. Twenty-eight mongrel dogs were used to measure for vascular cross-sectional area and average instantaneous peak velocity in the iliac arteries after the 5-min occlusion of the arteries. Postischemic vasodilatation was impaired after the infusion of Intralipid (20%, 2 ml/kg) and this impaired response was reversed by the co-administration of ascorbic acid (30 mg/kg). NG-monomethyl-L-arginine completely abolished postischemic vasodilatation. Plasma NOx levels were significantly reduced after the infusion of Intralipid compared with baseline (11.6+/-0.4 vs. 12.9+/-0.3 microM, p = 0.025) and after infusion of Intralipid with ascorbic acid compared with baseline (11.8+/-0.5 vs. 13.1+/-0.4 microM, p = 0.047). We concluded that ascorbic acid reverses the endothelial dysfunction induced by Intralipid without increasing plasma NOx- levels and that deactivation of nitric oxide by oxidative stress is a primary contributor to Intralipid-induced impaired vasodilation.

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

“…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 . Decreased endothelial nitric oxide production or deactivation of nitric oxide by oxidative stress was suggested to be the main mechanism for impairment of vasodilatation by Intralipid.…”

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

Systemic Blockage of Nitric Oxide Synthase by L-NAME Increases Left Ventricular Systolic Pressure, Which Is Not Augmented Further by Intralipid®

“…Intralipid ® emulsion attenuates endothelium-dependent nitric oxide-mediated relaxation in isolated vessels and induces endothelial dysfunction 13,14. In in vivo and ex vivo studies, intravenous infusion of Intralipid ® 20% or Lipofundin ® MCT/LCT 20% increases blood pressure or systemic vascular resistance 15-18.…”

Postprandial lipids accelerate and redirect nitric oxide consumption in plasma

“…Likewise, various plasma hydrophobic phases attenuate endothelial NO-mediated vasorelaxation in vivo [66; 67; 68; 69; 70; 71; 72; 73], and a similar inhibition is observed in vitro where triglyceride-rich lipoprotein micelles inhibit NO-dependent vasodilation of arteries suspended in tissue baths [27; 28; 29; 74; 75]. Studies such as these have also determined that the oxidation of TRL increases their vasoconstriction potential [31] and, interestingly, that NO and O 2 are about twice as diffusible in oxidized than native TRL [18].…”