A role for Rho kinase in vascular contraction evoked by sodium fluoride.
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.
Jeon
Su Bun
SB
Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Jin
Fanxue
F
Kim
Jee In
JI
Kim
Sang-Hyun
SH
Suk
Kyoungho
K
Chae
Shung Chull
SC
Jun
Jae Eun
JE
Park
Wee Hyun
WH
Kim
In Kyeom
IK
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D002352:Carrier Proteins / Q000378:metabolism; D004789:Enzyme Activation; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology*; D014661:Vasoconstriction; D054460:rho-Associated Kinases
D000577:Amides; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D012969:Sodium Fluoride; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D010749:Phosphoprotein Phosphatases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1