Vanadate causes synthesis of endothelium-derived NO via pertussis toxin- sensitive G protein in pigs

Ryuichi Nakaike, Hiroaki Shimokawa, M. Koji Owada, Osamu Tokunaga, Hiroshi Yasutake, Takuya Kishimoto, Chiharu Imada, Tadayoshi Shiraishi, Kensuke Egashira, Akira Takeshita

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Abstract

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(w)-nitro-L-arginine methyl ester. The relaxations were also abolished by pertussis toxin, an inhibitor of certain G proteins. Tyrosine kinase inhibitors, genistein and α-cyano-3- ethoxy-4-hydroxy-5-phenyl-methylcinnamamide (ST-638), significantly attenuated the vanadate-induced relaxations. Vanadate also caused pertussis toxins-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.

Original languageEnglish
Pages (from-to)H296-H302
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume271
Issue number1 40-1
Publication statusPublished - Jul 1 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Nakaike, R., Shimokawa, H., Owada, M. K., Tokunaga, O., Yasutake, H., Kishimoto, T., Imada, C., Shiraishi, T., Egashira, K., & Takeshita, A. (1996). Vanadate causes synthesis of endothelium-derived NO via pertussis toxin- sensitive G protein in pigs. American Journal of Physiology - Heart and Circulatory Physiology, 271(1 40-1), H296-H302.