Protamine relaxes vascular smooth muscle by directly reducing cytosolic free calcium concentrations in small resistance arteries

Takashi Akata, Kenji Kodama, Alex S. Evers, Shosuke Takahashi

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Protamine has been suggested to relax vascular smooth muscle by reducing the intracellular Ca2+ concentration ([Ca2+]i). However, there has been no direct evidence that protamine reduces the [Ca2+]i of vascular smooth muscle. We therefore studied the effects of protamine on changes in [Ca2+]i and tension induced by norepinephrine (NE) and high K+ in endothelium-denuded strips from rabbit small mesenteric artery, using fura-2-fluorometry and isometric tension recording methods. Both NE (1 μM) and high K+ (40 mM) produced a transient phasic increase, followed by a tonic increase in [Ca2+]i and tension. Protamine concentration (15-500 μg·ml-1)-dependently inhibited (P<0.05) the phasic and tonic components of both NE- and high K+-induced contraction with IC50 values of ≈50 μg·ml-1. Protamine (50 μg·ml-1) inhibited (P<0.05) the phasic and tonic increases in [Ca2+]i caused by both NE and high K+ by ≈40%-60%. We conclude that the direct vasodilator action of protamine is due, at least in part, to reduction of [Ca2+]i in vascular smooth muscle; this reduction in [Ca2+]i may be due to inhibition of both Ca2+ influx and Ca2+ release from intracellular Ca2+ stores.

Original languageEnglish
Pages (from-to)252-259
Number of pages8
JournalJournal of Anesthesia
Volume10
Issue number4
DOIs
StatePublished - Dec 1 1996

Keywords

  • Artery
  • Fura-2-fluorometry
  • Intracellular calcium concentration
  • Protamine
  • Resistance
  • Vascular smooth muscle

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