Neryl butyrate induces contractile effects on isolated preparations of rat aorta

Naunyn Schmiedebergs Arch Pharmacol. 2020 Jan;393(1):43-55. doi: 10.1007/s00210-019-01709-z. Epub 2019 Aug 16.

Abstract

Neryl butyrate is a constituent of volatile oils obtained from aromatic plants. Aliphatic organic compound analogues chemically close to neryl butyrate possess vasodilator properties in rat aorta. To evaluate whether neryl butyrate has relaxing properties, this study tested its effects on isolated rat aorta. Unlike the analogues, neryl butyrate did not show relaxant profile in aortic rings precontracted with phenylephrine, but induced a contraction when it stimulated aortic rings under resting tonus. The contractile effect augmented in endothelium-denuded aortic rings. Treatment of endothelium-intact preparations with the nitric oxide synthase inhibitor L-NAME or the guanylyl cyclase inhibitor ODQ also augmented the contractile effect of neryl butyrate. Such phenomenon was absent in the presence of the cyclooxygenase inhibitor indomethacin. Contractile responses decreased in the presence of verapamil, a L-type Ca2+ channel blocker, or when Ca2+ was removed from the extracellular solution. Antagonists of α-adrenergic receptors (prazosin and yohimbine), but not the thromboxane-prostanoid receptor seratrodast, reversed the contraction induced by neryl butyrate. The α1A selective antagonist RS-17053 antagonized the neryl butyrate-induced contraction. The contraction caused by neryl butyrate was decreased by inhibiting the phospholipase C or the rho-associated kinase with U-73122 or Y-27632, respectively. Injected intravenously to awake rats, neryl butyrate induced arterial hypotension and bradycardia. Decreased frequency was also present in isolated right atrium preparations. In conclusion, the contractile effects of neryl butyrate were inhibited by α-adrenergic antagonists, indicating the involvement of α-adrenoceptors in the mechanism of action. In vivo, neryl butyrate caused hypotension, suggesting that other systemic influence than vasoconstriction may occur.

Keywords: Adrenergic receptors; Monoterpenes; Thoracic aorta; Vascular endothelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Amides / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / physiology
  • Butyrates / pharmacology*
  • Calcium / pharmacology
  • Estrenes / pharmacology
  • Heart Atria / drug effects
  • In Vitro Techniques
  • Male
  • Phenylephrine / pharmacology
  • Phosphodiesterase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Pyridines / pharmacology
  • Pyrrolidinones / pharmacology
  • Rats, Wistar
  • Vasoconstriction / drug effects*
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Adrenergic alpha-Agonists
  • Amides
  • Butyrates
  • Estrenes
  • Phosphodiesterase Inhibitors
  • Protein Kinase Inhibitors
  • Pyridines
  • Pyrrolidinones
  • Vasoconstrictor Agents
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Y 27632
  • Phenylephrine
  • Calcium