Propionyl-L-carnitine dilates human subcutaneous arteries through an endothelium-dependent mechanism

Purpose: The vasoactive effects of propionyl-1-carnitine (PLC) on human arteries, including endothelial and smooth muscle cell influences, were studied. Methods: Small (less than 200 mu m) subcutaneous fat arteries (n = 19), obtained from human patients undergoing vascular surgery, were dissected and mounted in an arterio-graph system that allowed measurement of lumen diameter and control of transmural pressure. To investigate the role of the endothelium, arteries were compared intact, intact and in the presence of either 0.3 mmol/L nitro-1-arginine (an inhibitor of nitric oxide synthesis) or 10 mu mol/L indomethacin (an inhibitor of prostaglandin synthesis), or denuded of endothelium. After a 1-hour equilibration at a pressure of 50 mm Hg, arteries were precontracted 50% with an intermediate concentration of norepinephrine, and clinically relevant concentrations of PLC (0.1 to 100 mu mol/L) were cumulatively added to the bath while the lumen diameter was continually measured. Results: Intact arteries dose-dependently dilated to PLC, with the half maximal dilation occurring at 2.9 +/- 1.2 mu mol/L, increasing diameter 91% +/- 5% at 100 mu mol/L. In contrast, PLC had significantly less effect on deendothelialized arteries, increasing diameter only 24% +/- 11% at 100 mu mol/L (P < .01 vs. intact). This indicates the endothelial dependency of this compound. Blockade of nitric oxide did not inhibit this vasodilation, with the half-maximal response occurring at 8.6 +/- 7 mu mol/L, increasing diameter 85% +/- 8% at 100 mu mol/L (P > .05 vs, intact). However, this vasodilation was significantly diminished in the presence of indomethacin, which dilated arteries only 53% +/- 18% at 100 mu mol/L (P < .01 vs, intact; P > .05 vs. denuded). Conclusion: PLC is an endothelium-dependent vasodilator, the mechanism of which is partially mediated by prostaglandin synthesis, not nitric oxide. The beneficial effects of this compound may, in part, be related to vasodilation and enhanced blood flow.