L-carnitine may attenuate free fatty acid-induced endothelial dysfunction.
We have recently shown that elevated levels of free fatty acid (FFA) seen in insulin-resistant obese subjects are associated with endothelial dysfunction. L-carnitine, which is required for mitochondrial FFA transport/oxidation, has been reported to improve vascular function in subjects with diabetes and heart disease. Here, we tested the hypothesis that L-carnitine attenuates FFA-induced endothelial dysfunction. We studied leg blood flow (LBF) responses and leg vascular resistance (LVR) to graded intrafemoral artery infusions of the endothelium-dependent vasodilator, methacholine chloride (MCh). A group (n = 7) of normal lean subjects was studied under basal conditions (saline), after 2 h of FFA elevation (FFA), and then after 2 h of superimposing L-carnitine on FFA elevation. FFA elevation caused the maximal LBF increment in response to MCh to decrease from 0.388 +/- 0.08 to 0.212 +/- 0.071 L/min (P < 0.05). Similarly, FFA blunted the maximum decrease in LVR in response to MCh from -315 +/- 41 U to -105 +/- 46 U (P < 0.05). The superimposed L-carnitine restored the LBF increment in response to MCh to 0.488 +/- 0.088 L/min (P < 0.05 vs. FFA) and the maximum fall in LVR to -287 +/- 75 U (P < 0.05 vs. FFA), indicating that L-carnitine elevation may attenuate FFA-induced endothelial dysfunction. In conclusion, our data suggest that increasing L-carnitine levels may improve FFA-induced and obesity-associated endothelial dysfunction. This improved endothelial function may delay or prevent the development of excess cardiovascular disease.
Shankar
Sudha S
SS
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202-5111, USA.
Mirzamohammadi
Bahram
B
Walsh
James P
JP
Steinberg
Helmut O
HO
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D002331:Carnitine / Q000378:metabolism* / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007866:Leg / Q000098:blood supply; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology
D000925:Anticoagulants; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D010277:Parasympathomimetics; D016210:Methacholine Chloride; D006493:Heparin; D002331:Carnitine