Endothelin-1, an important mitogen of smooth muscle cells of spontaneously hypertensive rats.
- Author:
Gexiu LIU
1
;
Hua WANG
;
Daming OU
;
Honglin HUANG
;
Duanfang LIAO
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Division; drug effects; Cells, Cultured; DNA, Antisense; pharmacology; Dose-Response Relationship, Drug; Endothelin-1; pharmacology; Fibroblast Growth Factor 2; genetics; Gene Expression Regulation; drug effects; Muscle, Smooth, Vascular; cytology; drug effects; metabolism; Oligonucleotides; pharmacology; RNA, Messenger; drug effects; genetics; metabolism; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors
- From: Chinese Medical Journal 2002;115(5):750-752
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo study the features of vascular smooth muscle cell (VSMC) proliferation induced by endothelin-1 (ET-1).
METHODSVSMCs of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats were cultured and treated with ET-1. Basic fibroblast growth factor (bFGF) gene expression was measured using both Northern blot and an enzyme-linked immunoassay.
RESULTSET-1 resulted in an increase in bFGF transcripts at 8 - 24 h; bFGF levels were significantly higher in VSMCs treated with ET-1 than in those not treated. However, VSMCs growth responses in SHR and WKY were different. Smooth muscle cells of SHR were hyper-responsive to ET-1. Maximal bFGF mRNA levels were elevated 3.5-fold at 4 h of stimulation in WKY and 8-fold at 8h in SHR4. Moreover, the proliferation of VSMCs induced by ET-1 was inhibited by antisense phosphorothioate oligodeoxynucleotides (10 micromol/L AS-bFGF) but not sense bFGF oligomers at the same concentrations, being reduced by 80% in SHR and 40% in WKY vs control, respectively. Furthermore, the effect of AS-bFGF oligomers on SHR SMC proliferation is significantly greater than on WKY SMC proliferation.
CONCLUSIONET-1 may be required for exaggerated vascular growth responses in SHR and bFGF may be involved.
