A role for Rho kinase in vascular contraction evoked by sodium fluoride

Biochem Biophys Res Commun. 2006 Apr 28;343(1):27-33. doi: 10.1016/j.bbrc.2006.02.120. Epub 2006 Feb 28.

Abstract

Agonist and depolarization-induced vascular smooth muscle contractions involve the activation of Rho-kinase pathway. However, there are no reports addressing the question whether this pathway is involved in NaF-induced vascular contractions. We hypothesized that Rho-kinase plays a role in vascular contraction evoked by sodium fluoride in rat aortae. In both physiological salt solution and calcium-free solution with 2 mM EGTA, cumulative addition of NaF increased vascular tension in concentration-dependent manners. Effects of Rho-kinase inhibitor (Y27632) on phosphorylation of myosin light chain (MLC20) and myosin targeting subunit (MYPT1(Thr696)) of myosin light chain phosphatase as well as NaF-induced contractions were determined using isolated tissue and the Western blot experiments. Y27632 inhibited NaF-induced contractions in a concentration-dependent manner. NaF increased phosphorylation of MLC20 and MYPT1(Thr696), which were also inhibited by Y27632. However, MLCK inhibitor (ML-7) or PKC inhibitor (Ro31-8220) did not inhibit the NaF-induced contraction. These results indicate that activation of Rho-kinase and the subsequent phosphorylation of MYPT1(Thr696) play important roles in NaF-induced contraction of rat aortae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology
  • Animals
  • Aorta / drug effects*
  • Aorta / enzymology
  • Carrier Proteins / metabolism
  • Enzyme Activation
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Muscle Contraction*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / enzymology
  • Myosin Light Chains / metabolism
  • Myosin-Light-Chain Kinase / antagonists & inhibitors
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Phosphatase 1
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism*
  • Pyridines / pharmacology
  • Rats
  • Sodium Fluoride / pharmacology*
  • Vasoconstriction*
  • rho-Associated Kinases

Substances

  • Amides
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Myosin Light Chains
  • Protein Kinase Inhibitors
  • Pyridines
  • Y 27632
  • Sodium Fluoride
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases
  • Myosin-Light-Chain Kinase
  • Phosphoprotein Phosphatases
  • Ppp1r12a protein, rat
  • Protein Phosphatase 1