17beta-estradiol attenuates vascular contraction through inhibition of RhoA/Rho kinase pathway.
We hypothesized that 17beta-estradiol attenuates vascular contraction through inhibition of RhoA/Rho kinase pathway. Rat aortic rings were contracted with cumulative addition of U46619, NaF, KCl or PDBu 30 min after pretreatment with 17beta-estradiol (10, 30, and 100 microM) or vehicle. We measured the amount of GTP RhoA and the level of phosphorylation of the myosin light chain (MLC(20)), myosin phosphatase targeting subunit 1 (MYPT1) and PKC-potentiated inhibitory protein for heterotrimeric MLCP of 17 kDa (CPI17). Pretreatment with 17beta-estradiol dose-dependently inhibited the concentration-response curves in response to U46619, NaF or KCl, but not to PDBu. 17beta-Estradiol decreased not only the level of phosphorylation of MYPT1(Thr855) and CPI17(Thr38) as well as MLC(20), but also the activity of RhoA induced by U46619 or NaF. However, 17beta-estradiol did not affect the level of phosphorylation of CPI17 induced by PDBu. 17beta-Estradiol attenuates vascular contraction through inhibition of RhoA/Rho kinase pathway.
Yang
Enyue
E
Department of Pharmacology, Kyungpook National University School of Medicine, 101 Dongin-2-Ga, Daegu 700-422, Republic of Korea.
Jeon
Su Bun
SB
Baek
Inji
I
Chen
Zheng-Ai
ZA
Jin
Zheng
Z
Kim
In Kyeom
IK
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009124:Muscle Proteins; D018994:Myosin Light Chains / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors*
D004967:Estrogens; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D018994:Myosin Light Chains; C107507:PPP1R14A protein, human; D047428:Protein Kinase Inhibitors; D004958:Estradiol; D054460:rho-Associated Kinases; D010749:Phosphoprotein Phosphatases; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human; D020742:rhoA GTP-Binding Protein