[Anti-hypertensive effects of PPARgamma ligands through the inhibition of Rho/Rho kinase pathway].
Although PPARgamma ligands have an antihypertensive effect in vivo, the precise mechanism has not been fully elucidated. We examined their effects on Rho/Rho kinase pathway, a key regulator of vascular tone. In cultured rat aortic smooth muscle cells, Rho kinase activated by angiotensin II was suppressed by the pretreatment with pioglitazone and troglitazone. The roles of Vav, a GTP/GDP exchange factor upregulating Rho kinase activity, and SHP-2, protein tyrosine phosphatase that dephosphorylated Vav and subsequently inactivated Rho kinase were examined. Both pioglitazone and troglitazone upregulated SHP-2, particularly in the cytosolic fraction, and the SHP-2-bound Vav, and reduced the phosphorylation of Vav. These mechanisms may contribute to the hemodynamic, in addition to metabolic, action by PPARgamma ligands in hypertensive, metabolic syndrome.
Wakino
Shu
S
Department of Internal Medicine, School of Medicine, Keio University.
Hayashi
Koichi
K
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D047495:PPAR gamma / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D054460:rho-Associated Kinases
D000209:Acute-Phase Proteins; D000959:Antihypertensive Agents; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D047495:PPAR gamma; C010781:acute-phase protein rho; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat