Vanadate causes synthesis of endothelium-derived NO via pertussis toxin-sensitive G protein in pigs.
The effects of sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, on the endothelial nitric oxide (NO) pathway were studied in vitro. Vanadate caused endothelium-dependent relaxations in isolated porcine coronary arteries, which were abolished by N omega-nitro-L-arginine methyl ester. The relaxations were also abolished by pertussis toxin, an inhibitor of certain G proteins. Tyrosine kinase inhibitors, genistein and alpha-cyano-3-ethoxy-4-hydroxy-5-phenyl-methylcinnamamide (ST-638), significantly attenuated the vanadate-induced relaxations. Vanadate also caused pertussis toxin-sensitive, endothelium-dependent relaxations in isolated porcine renal and femoral arteries and jugular veins. Immunoblots, using an antibody to phosphotyrosines and to c-Src in native porcine aortic endothelial cells, respectively, showed that vanadate induced an elevation of phosphotyrosine proteins and a decrease in the amount of the active form of c-Src family kinases; both changes were markedly suppressed by cotreatment with ST-638. These results indicate that in porcine blood vessels, vanadate causes a synthesis of endothelium-derived NO for which endothelial tyrosine kinases and pertussis toxin-sensitive G protein are considered to be closely involved.
Nakaike
R
R
Research Institute of Angiocardiology, Kyushu University School of Medicine, Fukuoka, Japan.
Shimokawa
H
H
Owada
M K
MK
Tokunaga
O
O
Yasutake
H
H
Kishimoto
T
T
Imada
C
C
Shiraishi
T
T
Egashira
K
K
Takeshita
A
A
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D019833:Genistein; D015151:Immunoblotting; D007529:Isoflavones / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D037342:Pertussis Toxin; D010766:Phosphorylation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013440:Sulfides / Q000494:pharmacology; D013552:Swine; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D002934:Cinnamates; D007529:Isoflavones; D013440:Sulfides; D010566:Virulence Factors, Bordetella; C060747:ST 638; D009569:Nitric Oxide; D014638:Vanadates; D014443:Tyrosine; D001120:Arginine; D019833:Genistein; D019001:Nitric Oxide Synthase; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester