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. 1990 Jun;100(2):241–246. doi: 10.1111/j.1476-5381.1990.tb15789.x

Interactions of palmitoyl carnitine with the endothelium in rat aorta.

I A Dainty 1, M Bigaud 1, J C McGrath 1, M Spedding 1
PMCID: PMC1917412  PMID: 1696151

Abstract

1. Palmitoyl carnitine (10-1000 microM) resembled Bay K 8644 (10-1000 nM) in that it directly contracted rat aortic rings which were partially depolarized with K+ (12 mM). However, the effects of Bay K 8644 were reduced in the presence of endothelium whereas the presence of the endothelium hardly affected the palmitoyl carnitine-induced contractions, which occurred at high concentrations (greater than 10 microM). 2. Lower concentrations of palmitoyl carnitine (0.3-30 microM; EC50 1.1 microM), but not Bay K 8644, carnitine or palmitic acid, antagonized the relaxant effects of acetylcholine in rat aorta. The antagonism was specific for endothelium-dependent relaxations, in that the relaxations to ATP and the calcium ionophore A23187 were also non-competitively antagonized, albeit at slightly higher concentrations, whereas the direct relaxant effects of sodium nitroprusside were unaffected. Palmitoyl carnitine therefore antagonizes the effects or the release of endothelial-derived relaxant factor (EDRF). The inhibitory effects were reversed on prolonged washout, indicating that the effects were not due to destruction of the endothelial cells. 3. In superfusion experiments, palmitoyl carnitine inhibited the release of EDRF from rat aorta but did not affect the responsiveness to exogenous EDRF, indicating a site of action at the endothelial cell. In superfusion experiments, palmitoyl carnitine, and lysophosphatidyl choline, caused direct relaxations of the aorta, indicating EDRF release, prior to inhibition of release evoked by receptor stimulation. These substances may modulate vascular responsiveness under certain conditions.

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Selected References

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  1. Busselen P., Sercu D., Verdonck F. Exogenous palmitoyl carnitine and membrane damage in rat hearts. J Mol Cell Cardiol. 1988 Oct;20(10):905–916. doi: 10.1016/s0022-2828(88)80145-7. [DOI] [PubMed] [Google Scholar]
  2. Corr P. B., Gross R. W., Sobel B. E. Amphipathic metabolites and membrane dysfunction in ischemic myocardium. Circ Res. 1984 Aug;55(2):135–154. doi: 10.1161/01.res.55.2.135. [DOI] [PubMed] [Google Scholar]
  3. Corr P. B., Snyder D. W., Cain M. E., Crafford W. A., Jr, Gross R. W., Sobel B. E. Electrophysiological effects of amphiphiles on canine purkinje fibers. Implications for dysrhythmia secondary to ischemia. Circ Res. 1981 Aug;49(2):354–363. doi: 10.1161/01.res.49.2.354. [DOI] [PubMed] [Google Scholar]
  4. Corr P. B., Snyder D. W., Lee B. I., Gross R. W., Keim C. R., Sobel B. E. Pathophysiological concentrations of lysophosphatides and the slow response. Am J Physiol. 1982 Aug;243(2):H187–H195. doi: 10.1152/ajpheart.1982.243.2.H187. [DOI] [PubMed] [Google Scholar]
  5. Fink K. L., Gross R. W. Modulation of canine myocardial sarcolemmal membrane fluidity by amphiphilic compounds. Circ Res. 1984 Nov;55(5):585–594. doi: 10.1161/01.res.55.5.585. [DOI] [PubMed] [Google Scholar]
  6. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  7. Griffith T. M., Edwards D. H., Newby A. C., Lewis M. J., Henderson A. H. Production of endothelium derived relaxant factor is dependent on oxidative phosphorylation and extracellular calcium. Cardiovasc Res. 1986 Jan;20(1):7–12. doi: 10.1093/cvr/20.1.7. [DOI] [PubMed] [Google Scholar]
  8. Gryglewski R. J., Palmer R. M., Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1986 Apr 3;320(6061):454–456. doi: 10.1038/320454a0. [DOI] [PubMed] [Google Scholar]
  9. Idell-Wenger J. A., Grotyohann L. W., Neely J. R. Coenzyme A and carnitine distribution in normal and ischemic hearts. J Biol Chem. 1978 Jun 25;253(12):4310–4318. [PubMed] [Google Scholar]
  10. Inoue D., Pappano A. J. L-palmitylcarnitine and calcium ions act similarly on excitatory ionic currents in avian ventricular muscle. Circ Res. 1983 Jun;52(6):625–634. doi: 10.1161/01.res.52.6.625. [DOI] [PubMed] [Google Scholar]
  11. Knabb M. T., Saffitz J. E., Corr P. B., Sobel B. E. The dependence of electrophysiological derangements on accumulation of endogenous long-chain acyl carnitine in hypoxic neonatal rat myocytes. Circ Res. 1986 Feb;58(2):230–240. doi: 10.1161/01.res.58.2.230. [DOI] [PubMed] [Google Scholar]
  12. Liedtke A. J., Nellis S., Neely J. R. Effects of excess free fatty acids on mechanical and metabolic function in normal and ischemic myocardium in swine. Circ Res. 1978 Oct;43(4):652–661. doi: 10.1161/01.res.43.4.652. [DOI] [PubMed] [Google Scholar]
  13. Loeb A. L., Izzo N. J., Jr, Johnson R. M., Garrison J. C., Peach M. J. Endothelium-derived relaxing factor release associated with increased endothelial cell inositol trisphosphate and intracellular calcium. Am J Cardiol. 1988 Oct 5;62(11):36G–40G. doi: 10.1016/0002-9149(88)90030-6. [DOI] [PubMed] [Google Scholar]
  14. Neely J. R., Feuvray D. Metabolic products and myocardial ischemia. Am J Pathol. 1981 Feb;102(2):282–291. [PMC free article] [PubMed] [Google Scholar]
  15. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  16. Patmore L., Duncan G. P., Spedding M. Interaction of palmitoyl carnitine with calcium antagonists in myocytes. Br J Pharmacol. 1989 Jun;97(2):443–450. doi: 10.1111/j.1476-5381.1989.tb11971.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rubanyi G. M., Schwartz A., Vanhoutte P. M. The calcium agonists Bay K 8644 and (+)202,791 stimulate the release of endothelial relaxing factor from canine femoral arteries. Eur J Pharmacol. 1985 Oct 29;117(1):143–144. doi: 10.1016/0014-2999(85)90485-6. [DOI] [PubMed] [Google Scholar]
  18. Rubanyi G. M., Vanhoutte P. M. Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J Physiol. 1985 Jul;364:45–56. doi: 10.1113/jphysiol.1985.sp015728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saito T., Wolf A., Menon N. K., Saeed M., Alves C., Bing R. J. Lysolecithins as endothelium-dependent vascular smooth muscle relaxants that differ from endothelium-derived relaxing factor (nitric oxide) Proc Natl Acad Sci U S A. 1988 Nov;85(21):8246–8250. doi: 10.1073/pnas.85.21.8246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Spedding M., Mir A. K. Direct activation of Ca2+ channels by palmitoyl carnitine, a putative endogenous ligand. Br J Pharmacol. 1987 Oct;92(2):457–468. doi: 10.1111/j.1476-5381.1987.tb11343.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Spedding M., Schini V., Schoeffter P., Miller R. C. Calcium channel activation does not increase release of endothelial-derived relaxant factors (EDRF) in rat aorta although tonic release of EDRF may modulate calcium channel activity in smooth muscle. J Cardiovasc Pharmacol. 1986 Nov-Dec;8(6):1130–1137. doi: 10.1097/00005344-198611000-00006. [DOI] [PubMed] [Google Scholar]
  22. Takeda K., Schini V., Stoeckel H. Voltage-activated potassium, but not calcium currents in cultured bovine aortic endothelial cells. Pflugers Arch. 1987 Nov;410(4-5):385–393. doi: 10.1007/BF00586515. [DOI] [PubMed] [Google Scholar]

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