Vascular smooth muscle cell hyper-responsiveness to growth factors in hypertension

To understand the intrinsic mechanisms of vascular smooth muscle cell proliferation, we studied the growth of cultured rat aortic smooth muscle from spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto rats (WKY), under basal conditions and after stimulation. Cell growth was assessed by the determination of cell number, and incorporation of 3H-thymidine into newly-synthesized DNA. We demonstrated that vascular smooth muscle cells from SHR proliferate faster and grow to a greater density, regardless of the initial plating number. The growth difference was not due to different plating efficiencies. Significantly higher 3H-thymidine incorporation was observed in vascular smooth muscle cells from SHR when the cells were stimulated by calf serum, platelet-derived growth factor or epidermal growth factor. Exposure to calf serum elicited an excessive expression of c-myc and c-fos in the first hour after stimulation. These results provide evidence of the hyper-responsiveness of vascular smooth muscle cells from SHR aortae to growth stimuli.