Growth regulation in smooth muscle cells from normal and hypertensive rats

Smooth muscle cell proliferation is regulated through the coordinated interaction of growth factors/mitogens and growth inhibitors such as heparin. Vascular smooth muscle cells isolated from the thoracic aorta of adult male spontaneously hypertensive rats (SHR) proliferated faster and reached higher cell densities during 8-day culture periods than cells isolated from age- and sex-matched Wistar-Kyoto (WKY) animals. Since both cell isolates were exposed to the same array of growth factors present in fetal calf serum, the differences in proliferation rates were indicative of a differential responsiveness between the two cell types to such factors. Cultures from SHR and WKY rendered quiescent by serum withdrawal were shown to respond to epidermal growth factor in a differential manner, whereas they exhibited similar responsiveness to platelet-derived growth factor and somatomedin C. Cells from hypertensive animals expressed twice as many specific cell surface receptors for epidermal growth factor as their normotensive counterparts. However, in contrast the latter possessed double the number of specific cell surface heparin binding sites when compared to cells from hypertensive animals. The coordinated interaction of heparin epidermal growth factor and extracellular matrix thrombospondin may be a mechanism for vascular smooth muscle growth regulation.