Lipid emulsion inhibits the vasodilation induced by a toxic dose of amlodipine in isolated rat aortae

Int J Med Sci. 2019 Nov 9;16(12):1621-1630. doi: 10.7150/ijms.38502. eCollection 2019.

Abstract

The goal of this study was to examine the effect of lipid emulsion on the vasodilation induced in isolated endothelium-denuded rat aortae by a toxic dose of amlodipine. We examined the effects of lipid emulsion and verapamil on amlodipine-induced vasodilation. We also examined the effects of a mixture of lipid emulsion and amlodipine, as well as the centrifuged aqueous extract (CAE) obtained by ultracentrifuging such a mixture and then removing the upper lipid layer, on amlodipine-induced vasodilation. The effect of lipid emulsion on the amlodipine concentration was examined. Lipid emulsion attenuated amlodipine-induced vasodilation in isolated aortae. Both CAE and lipid emulsion containing amlodipine inhibited amlodipine-induced vasodilation. However, there was no significant difference in amlodipine-induced vasodilation between aortae treated with CAE and those treated with lipid emulsion containing amlodipine. Verapamil inhibited amlodipine-induced vasodilation. Lipid emulsion decreased the concentration of amlodipine. Lipid emulsion attenuated the vasodilation induced by a toxic amlodipine dose in NaF-precontracted aortae. The data show that lipid emulsion inhibited the vasodilation induced by a toxic amlodipine dose in isolated rat aortae by reducing the concentration of amlodipine. Amlodipine-induced vasodilation seems to be mediated mainly by blockade of L-type calcium channels and partially by inhibition of the Rho-kinase pathway.

Keywords: amlodipine; centrifuged aqueous extract; lipid emulsion; vasodilation; verapamil.

MeSH terms

  • Amlodipine / pharmacology*
  • Amlodipine / toxicity
  • Animals
  • Aorta / drug effects*
  • Aorta / physiopathology
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / genetics
  • Emulsions / pharmacology
  • Humans
  • Lipids / antagonists & inhibitors
  • Lipids / chemistry
  • Lipids / pharmacology*
  • Male
  • Organ Culture Techniques
  • Rats
  • Signal Transduction / drug effects
  • Vasodilation / drug effects*
  • Vasodilation / genetics
  • Vasodilation / physiology
  • Verapamil / pharmacology
  • rho-Associated Kinases / genetics

Substances

  • Calcium Channels, L-Type
  • Emulsions
  • Lipids
  • Amlodipine
  • Verapamil
  • rho-Associated Kinases