Vanadate causes the synthesis of endothelium-derived nitric oxide
via pertussis toxin-sensitive g-protein in pigs.
Nakaike, Ryuichi, Hiroaki Shimokawa, M. Koji Owada, Osamu Tokunaga,
Hiroshi Yasutake, Takuya Kishimoto, Chiharu Imada, Tadayoshi
Shiraishi, Kensuke Egashira, Akira Takeshita.
Research Institute of Angiocardiology and Cardiovascular Clinic,
Kyushu University School of Medicine, Fukuoka, Japan, Institute of
Molecular and Cellular Biology for Pharmaceutical Science, Kyoto
Pharmaceutical University, Kyoto, Japan, Department of Pathology,
Saga Medical University, Saga, Japan, and Biochemical Research
Laboratories, Kanegafuchi Chemical Industry Co.,Ltd., Takasago,
Hyogo, Japan
APStracts 3:0060H, 1996.
The effects of sodium orthovanadate, an inhibitor of protein tyrosine
phosphatases, on the endothelial nitric oxide pathway were studied in
vitro. Vanadate caused endothelium-dependent relaxations in isolated
porcine coronary arteries, which were abolished by Nwnitro-L-arginine
methyl ester. The relaxations were also abolished by pertussis toxin,
an inhibitor of certain G-proteins. Tyrosine kinase inhibitors,
genistein and 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. Immunoblotting 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 active form
of c-Src family kinases; both changes were markedly suppressed by co
-treatment with ST-638. These results indicate that in porcine blood
vessels, vanadate causes a synthesis of endothelium-derived nitric
oxide, for which endothelial tyrosine kinases and pertussis toxin
-sensitive G-protein are considered to be closely involved.
Received 2 May 1995; accepted in final form 24 January 1996.
APS Manuscript Number H418-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96