Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the angiotensin II type-1 receptor: implication in vascular migration.
BACKGROUND
Although, endothelial nitric oxide (NO) synthase (eNOS) is believed to antagonize vascular remodeling induced by the angiotensin II (AngII) type-1 receptor, the exact signaling mechanism remains unclear.


RESULTS
By expressing eNOS to vascular smooth muscle cells (VSMCs) via adenovirus, we investigated a signal transduction mechanism of the eNOS gene transfer in preventing vascular remodeling induced by AngII. We found marked inhibition of AngII-induced Rho/Rho-kinase activation and subsequent VSMC migration by eNOS gene transfer whereas G(q)-dependent transactivation of the epidermal growth factor receptor by AngII remains intact. This could be explained by the specific inhibition of G(12/13) activation by eNOS-mediated G(12/13) phosphorylation.


CONCLUSIONS
The eNOS/NO cascade specifically targets the Rho/Rho-kinase system via inhibition of G(12/13) to prevent vascular migration induced by AngII, representing a novel signal cross-talk in cardiovascular protection by NO.
Suzuki
Hiroyuki
H
Cardiovascular Research Center, Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Kimura
Keita
K
Shirai
Heigoro
H
Eguchi
Kunie
K
Higuchi
Sadaharu
S
Hinoki
Akinari
A
Ishimaru
Kazuhiro
K
Brailoiu
Eugen
E
Dhanasekaran
Danny N
DN
Stemmle
Laura N
LN
Fields
Timothy A
TA
Frank
Gerald D
GD
Autieri
Michael V
MV
Eguchi
Satoru
S
D000256:Adenoviridae / Q000235:genetics; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002465:Cell Movement; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology; D066246:ErbB Receptors / Q000378:metabolism; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D005822:Genetic Vectors; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014161:Transduction, Genetic; D054460:rho-Associated Kinases / Q000378:metabolism*
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D066246:ErbB Receptors; D054460:rho-Associated Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D006152:Cyclic GMP