Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1990 Mar;99(3):477–480. doi: 10.1111/j.1476-5381.1990.tb12953.x

The effects of novel vasodilator long chain acyl carnitine esters in the isolated perfused heart of the rat.

D N Criddle 1, G H Dewar 1, W B Wathey 1, B Woodward 1
PMCID: PMC1917345  PMID: 1691947

Abstract

1. The effects of palmitoyl carnitine (PC) and novel derivatives were examined on the isolated Langendorff perfused heart of the rat. 2. Bolus injections of PC (1-300 nmol) produced coronary constriction accompanied by a cumulative irreversible depression of contractility. 3. Prior storage of PC in chloroform containing 2% ethanol in heat-sealed ampoules resulted in production of the ethyl ester of the compound (PCE). This compound was isolated and also synthesized (P1E). In contrast to PC, both PCE and P1E exhibited potent vasodilator activity. 4. Increasing the fatty acid chain length from palmitoyl to stearoyl resulted in a significant reduction in coronary dilator activity of the ester compound, whereas different ester groups did not affect the vasodilator action appreciably. Complete removal of the fatty acid chain abolished all vascular effects at the doses used. 5. The vasodilatation produced by these acyl carnitine esters was comparable to that produced by several known vasodilator drugs including verapamil, cromakalim, amyl nitrate and iloprost; however, the duration of the vasodilator response was more prolonged with the carnitate derivatives.

Full text

PDF
479

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams R. J., Cohen D. W., Gupte S., Johnson J. D., Wallick E. T., Wang T., Schwartz A. In vitro effects of palmitylcarnitine on cardiac plasma membrane Na,K-ATPase, and sarcoplasmic reticulum Ca2+-ATPase and Ca2+ transport. J Biol Chem. 1979 Dec 25;254(24):12404–12410. [PubMed] [Google Scholar]
  2. Baydoun A. R., Markham A., Morgan R. M., Sweetman A. J. Palmitoyl carnitine: an endogenous promotor of calcium efflux from rat heart mitochondria. Biochem Pharmacol. 1988 Aug 15;37(16):3103–3107. doi: 10.1016/0006-2952(88)90307-3. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Corr P. B., Shayman J. A., Kramer J. B., Kipnis R. J. Increased alpha-adrenergic receptors in ischemic cat myocardium. A potential mediator of electrophysiological derangements. J Clin Invest. 1981 Apr;67(4):1232–1236. doi: 10.1172/JCI110139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Heathers G. P., Yamada K. A., Kanter E. M., Corr P. B. Long-chain acylcarnitines mediate the hypoxia-induced increase in alpha 1-adrenergic receptors on adult canine myocytes. Circ Res. 1987 Nov;61(5):735–746. doi: 10.1161/01.res.61.5.735. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Levitsky D. O., Skulachev V. P. Carnitine: the carrier transporting fatty acyls into mitochondria by means of an electrochemical gradient of H + . Biochim Biophys Acta. 1972 Jul 12;275(1):33–50. doi: 10.1016/0005-2728(72)90022-9. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Nakaya H., Tohse N. Electrophysiological effects of acetyl glyceryl ether phosphorylcholine on cardiac tissues: comparison with lysophosphatidylcholine and long chain acyl carnitine. Br J Pharmacol. 1986 Dec;89(4):749–757. doi: 10.1111/j.1476-5381.1986.tb11179.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Vanhoutte P. M., Miller V. M. Heterogeneity of endothelium-dependent responses in mammalian blood vessels. J Cardiovasc Pharmacol. 1985;7 (Suppl 3):S12–S23. doi: 10.1097/00005344-198500073-00002. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES