Selectively Enhanced Stimulation of Dna Synthesis by Egf in Vascular Smooth Muscle Cells from Young and Adult Shr

Abstract

Aortic vascular smooth muscle cells isolated from spontaneously hypertensive rats (SHR) replicatein vitro nearly twice as fast as cells isolated from several normotensive control strains of rats. Serum-derived peptide growth factors are known to stimulate cells to enter the DNA synthetic phase of the cell cycle and subsequent mitosis. We have examined the effect of several peptide growth factors to stimulate [³H]thymidine incorporation into DNA in smooth muscle cells isolated from adult (24 wk, hypertensive) SHR and age matched normotensive NIH Black Wistar (NBR) control rats. Our results indicate that the response of the SHR cells to epidermal growth factor (EGF) is selectively enhanced compared to the control NBR cells. PDGF also stimulated DNA synthesis but no significant difference between SHR and NBR was observed. Nerve growth factor and endothelial derived growth factor were not mitotic on either cell line. Additionally, we have found that SHR cells, isolated from young early hypertensive weanling animals before a significant elevation in pressure has occurred, divide at the same rate as adult SHR cells and also exhibit the same enhanced EGF effect when compared to the young or adult normotensive strains. These results are consistent with the view that genetic changes affecting the cellular response to EGF may influence the development of early hypertensive hyperplasia in the SHR which in concert with other factors aggravates the later development of hypertension.

Key Words:

• Vascular smooth muscle
• DNA synthesis
• peptide growth factors
• hyperplasia
• SHR