Inhibition of extracellular signal-regulated kinases ameliorates hypertension-induced renal vascular remodeling in rat models.

Abstract

The aim of this study is to investigate the effect of the extracellular signal-regulated kinases 1/2 (ERK1/2) inhibitor, PD98059, on high blood pressure and related vascular changes. Blood pressure was recorded, thicknesses of renal small artery walls were measured and ERK1/2 immunoreactivity and erk2 mRNA in renal vascular smooth muscle cells (VSMCs) and endothelial cells were detected by immunohistochemistry and in situ hybridization in normotensive wistar kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and PD98059-treated SHR. Compared with normo-tensive WKY rats, SHR developed hypertension at 8 weeks of age, thickened renal small artery wall and asymmetric arrangement of VSMCs at 16 and 24 weeks of age. Phospho-ERK1/2 immunoreactivity and erk2 mRNA expression levels were increased in VSMCs and endothelial cells of the renal small arteries in the SHR. Treating SHR with PD98059 reduced the spontaneous hypertension-induced vascular wall thickening. This effect was associated with suppressions of erk2 mRNA expression and ERK1/2 phosphorylation in VSMCs and endothelial cells of the renal small arteries. It is concluded that inhibition of ERK1/2 ameliorates hypertension induced vascular remodeling in renal small arteries.

• Authors: Li Jing, Jianzhong Zhang, Jinping Sun, Fengying Guo, Xin An, Kan Yang, Ping Andy Li
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 12 Issue 12 Pg. 8333-46 ( 2011) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 22272075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavonoids
• Protein Kinase Inhibitors
• RNA, Messenger
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Endothelium, Vascular (metabolism)
• Female
• Flavonoids (pharmacology, therapeutic use)
• Hypertension (drug therapy, metabolism, pathology)
• MAP Kinase Signaling System
• Male
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, genetics, metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Renal Artery (drug effects, metabolism, pathology)
• Vascular Remodeling (drug effects)