Endothelin-1, an important mitogen of smooth muscle cells of spontaneously hypertensive rats.
OBJECTIVE
To study the features of vascular smooth muscle cell (VSMC) proliferation induced by endothelin-1 (ET-1).


METHODS
VSMCs 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.


RESULTS
ET-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.


CONCLUSIONS
ET-1 may be required for exaggerated vascular growth responses in SHR and bFGF may be involved.
Institute of Pharmacy & Pharmacology of Nanhua University, Hengyang 421001, China. gxliu27@china.com
Gexiu
G
Liu
Hua
H
Wang
Daming
D
Ou
Honglin
H
Huang
Duanfang
D
Liao
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016373:DNA, Antisense / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D016373:DNA, Antisense; D019332:Endothelin-1; D009841:Oligonucleotides; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2