Effects of Estradiol and Its Metabolites on Glomerular Endothelial Nitric Oxide Synthesis and Mesangial Cell Growth

Reduced nitric oxide synthesis by glomerular endothelial cells and increased proliferation of glomerular mesangial cells is associated with glomerular remodeling that leads to accelerated glomerulosclerosis. Estradiol induces nitric oxide synthesis and slows the progression of renal disease. Because...

Full description

Saved in:
Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2001-02, Vol.37 (2, Part 2 Suppl), p.645-650
Main Authors: Xiao, Shen, Gillespie, Delbert G, Baylis, Christine, Jackson, Edwin K, Dubey, Raghvendra K
Format: Article
Language:English
Subjects:
2-Methoxyestradiol
Biological and medical sciences
Blood vessels and receptors
Cell Division - drug effects
Cells, Cultured
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Estradiol - analogs & derivatives
Estradiol - metabolism
Estradiol - pharmacology
Fulvestrant
Fundamental and applied biological sciences. Psychology
Glomerular Mesangium - drug effects
Glomerular Mesangium - metabolism
Glomerulosclerosis, Focal Segmental - etiology
Humans
Kidney Glomerulus - drug effects
Kidney Glomerulus - metabolism
Nitric Oxide - metabolism
Nitric Oxide Synthase - metabolism
Progestins - pharmacology
Receptors, Estrogen - antagonists & inhibitors
Vertebrates: cardiovascular system
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Reduced nitric oxide synthesis by glomerular endothelial cells and increased proliferation of glomerular mesangial cells is associated with glomerular remodeling that leads to accelerated glomerulosclerosis. Estradiol induces nitric oxide synthesis and slows the progression of renal disease. Because the estradiol metabolites 2-hydroxyestradiol and 2-methoxyestradiol are more potent than estradiol in inhibiting growth of vascular smooth muscle cells, which are phenotypically similar to mesangial cells, we compared the effects of estradiol, 2-hydroxyestradiol, and 2-methoxyestradiol on growth of glomerular mesangial cells and on basal nitric oxide synthesis by glomerular endothelial cells. In human glomerular mesangial cells, estradiol and its metabolites concentration-dependently (1 nmol/L to 10 μmol/L) inhibited serum (2.5%)-induced DNA synthesis, cell proliferation, and collagen synthesis with the order of potency being 2-methoxyestradiol > 2-hydroxyestradiol > estradiol. ICI182780 (100 μmol/L, an estrogen receptor antagonist) blocked the growth inhibitory effects of estradiol but not 2-hydroxyestradiol or 2-methoxyestradiol. Treatment with estradiol, but not 2-hydroxyestradiol and 2-methoxyestradiol, induced nitric oxide synthesis (P
ISSN:0194-911X
1524-4563
DOI:10.1161/01.HYP.37.2.645