Differential Suppressive Effects of Rho Kinase Inhibitor Fasudil on Serotonin- and Noradrenaline-Induced Contractions of Human Internal Thoracic Arteries and Saphenous Veins

Biol Pharm Bull. 2024;47(10):1657-1661. doi: 10.1248/bpb.b24-00502.

Abstract

Rho kinase inhibitor fasudil exerts therapeutic effects against vasospasms. In this study, we aimed to compare its suppressive effects on serotonin (5-HT)- and noradrenaline (NAd)-induced contractions of human endothelium-denuded internal thoracic arteries (ITAs) and saphenous veins (SVs). NAd and 5-HT induced concentration-dependent contractions in both ITAs and SVs. However, fasudil (3 µmol/L) pretreatment decreased these constrictor-induced contractions in both ITAs and SVs. Fasudil exerted similar inhibitory effects on 5-HT and NAd in ITAs. However, in SVs, fasudil exerted stronger inhibitory effects on NAd-induced contractions than on 5-HT-induced contractions. Therefore, inhibitory effects of fasudil on 5-HT-induced contractions were stronger in ITAs than in SVs. Overall, these results suggest that Rho kinases exert different effects on the two vasoconstrictors in SVs, but not in ITAs, thus explaining their different graft patencies.

Keywords: fasudil; internal thoracic artery; noradrenaline; saphenous vein; serotonin.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine* / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine* / pharmacology
  • Female
  • Humans
  • Male
  • Mammary Arteries / drug effects
  • Middle Aged
  • Norepinephrine / pharmacology
  • Protein Kinase Inhibitors* / pharmacology
  • Saphenous Vein* / drug effects
  • Serotonin / pharmacology
  • Vasoconstriction / drug effects
  • Vasoconstrictor Agents / pharmacology
  • rho-Associated Kinases* / antagonists & inhibitors
  • rho-Associated Kinases* / metabolism

Substances

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • fasudil
  • Norepinephrine
  • Protein Kinase Inhibitors
  • rho-Associated Kinases
  • Serotonin
  • Vasoconstrictor Agents