Endothelin-1, an important mitogen of smooth muscle cells of spontaneously hypertensive rats
Liu, G.; Wang, H.; Ou, D.; Huang, H.; Liao, D.
Chinese Medical Journal 115(5): 750-752
2002
ISSN/ISBN: 0366-6999 PMID: 12133549 Document Number: 544877
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 mumol/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. Conclusion: ET-1 may be required for exaggerated vascular growth responses in SHR and bFGF may be involved.