Enhanced growth and growth factor responsiveness of vascular smooth muscle cells from hypertensive rats

Vascular smooth muscle cells from spontaneously hypertensive rats (SHR) exhibited enhanced growth rates in culture when compared to cells from their normotensive, Wistar-Kyoto (WKY) counterparts. Proliferation rates were dependent on supplementation levels of fetal calf serum (FCS) in culture medium and the passage number of the cells studied. Cells from hypertensive animals were more responsive to a number of agonists, as assessed by activation of S6 kinase and elevation of intracellular pH than those derived from WKY animals. Furthermore, SHR-derived cells exhibited enhanced turnover of phosphoinositides when exposed to epidermal growth factor or angiotensin II as compared to cells from normotensive rats treated in the same way. The latter cells were, however, more susceptible to growth inhibition by heparin than their hypertensive counterparts and possessed twice the number of specific cell surface heparin receptors as SHR-derived cells. Both cell types showed a marked stimulation of proliferation rates when they were cultured on extracellular matrix coated plasticware. Matrices elaborated by SHR-derived cells were more stimulatory to growth than those derived from WKY sources.