Lipofundin MCT/LCT Inhibits Levcromakalim-Induced Vasodilation by Inhibiting Endothelial Nitric Oxide Release

• Published in: International journal of molecular sciences 2020-03, Vol.21 (5), p.1763
• Main Authors: Lee, Soo Hee, Kang, Dawon, Ok, Seong-Ho, Kim, Ji-Yoon, Bae, Sung Il, Hwang, Yeran, Park, Kyeong-Eon, Kim, Jong Won, Sohn, Ju-Tae
• Format: Article
• Language: English
• Subjects: Animals; Aorta; Aorta - metabolism; Arginine; atp-sensitive potassium channel; Blood pressure; Cromakalim; Cyclic GMP; Cyclic GMP - metabolism; Drug Combinations; Emulsions; Endothelial Cells - metabolism; Endothelium; Fatty acids; Fatty Acids - chemistry; Glibenclamide; Guanosine; Hyperpolarization; Kinases; levcromakalim; lipid emulsion; Lipids; Male; Membrane Potentials; NG-Nitroarginine methyl ester; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Nitroarginine; Phospholipids - pharmacology; Phosphorylation; Potassium; Potassium channels; Potassium Channels - metabolism; Rats; Rats, Sprague-Dawley; Sorbitol - pharmacology; Toxicity; Vasodilation; Vasodilation - drug effects
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21051763

The goal of this study was to examine the effect of lipid emulsion on the vasodilation induced by ATP-sensitive potassium (K ) channels in isolated rat aortae and the underlying mechanism. The effects of Intralipid, containing 100% long-chain fatty acids, and Lipofundin MCT/LCT, containing 50% long-chain fatty acids plus 50% medium-chain fatty acids, on the vasodilation induced by levcromakalim in endothelium-intact aorta with or without N -nitro-L-arginine methyl ester (L-NAME) and in endothelium-denuded aorta were examined. The effects of L-arginine, L-NAME, glibenclamide, and Lipofundin MCT/LCT, alone or combined, on the levcromakalim-induced vasodilation were examined. Lipofundin MCT/LCT inhibited the levcromakalim-induced vasodilation of isolated endothelium-intact aortae, whereas Intralipid did not. In addition, Lipofundin MCT/LCT had no effect on the levcromakalim-induced vasodilation of endothelium-denuded rat aortae and endothelium-intact aortae with L-NAME. L-arginine and Lipofundin MCT/LCT produced more levcromakalim-induced vasodilation than Lipofundin MCT/LCT alone. Glibenclamide inhibited levcromakalim-induced vasodilation. Levcromakalim did not significantly alter endothelial nitric oxide synthase phosphorylation, whereas Lipofundin MCT/LCT decreased cyclic guanosine monophosphate. Lipofundin MCT/LCT did not significantly alter levcromakalim-induced membrane hyperpolarization. Taken together, these results suggest that Lipofundin MCT/LCT inhibits the vasodilation induced by levcromakalim by inhibiting basally released endothelial nitric oxide, which seems to occur through medium-chain fatty acids.