DIFFERENCES IN GROWTH-CHARACTERISTICS OF VASCULAR SMOOTH-MUSCLE FROM SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS ARE GROWTH-FACTOR DEPENDENT

Objective: To investigate whether the differences in the growth proper ties between vascular smooth muscle cells (VSMC) from spontaneously hy pertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats depend on the type and nature of the growth factor. Design: The growth charac teristics of VSMC from SHR and WKY rats were compared in the presence of different growth factors. These were related to growth factor recep tor expression on the VSMC. Methods: Growth rates, cell densities at w hich VSMC become quiescent and [H-3]-thymidine incorporation into DNA were examined in VSMC from SHR and WKY rats following exposure to epid ermal growth factor (EGF), basic fibroblast growth factor (bFGF) or th e three isoforms of platelet-derived growth factor (PDGF-AA, PDGF-AB a nd PDGF-BB). Receptor expression (receptor binding and Northern analys is) for these growth factors was also examined on VSMC from the two st rains.Results: VSMC from SHR exposed to the individual growth factors exhibited growth rates higher than those from WKY rats. For EGF, bFGF, PDGF-AB and PDGF-BB there was no difference in the sensitivity of VSM C to stimulation of [H-3]-thymidine incorporation between the strains. In contrast, VSMC from SHR exhibited significantly increased sensitiv ity to the mitogenic effects of PDGF-AA. VSMC from SHR exposed to PDGF -BB or EGF proliferated and then became quiescent at densities approxi mately 50 and 200% higher, respectively, than those from WKY rats. In contrast, in the presence of bFGF, proliferating VSMC from WKY rats be came quiescent at densities approximately 20% higher than those from S HR. Scatchard analysis of [I-125]-labelled growth factor binding to VS MC from the two strains revealed similar receptor numbers and dissocia tion constants for all growth factors. Steady-state messenger RNA leve ls for the different receptors were also similar and could not account for the enhanced growth rates of VSMC from SHR. Conclusion: The rate and magnitude of the proliferative response elicited in VSMC cultures from SHR and WKY rats is critically dependent on the nature of the gro wth factor stimulus.