Abnormalities in growth characteristics of aortic smooth muscle cells in spontaneously hypertensive rats.

Abstract

Comparative studies have shown that cultured vascular smooth muscle cells from spontaneously hypertensive rats (SHR) proliferate to a higher cell number, grow to a greater density, and have greater specific growth rate, particularly at a higher saturation density, than those of the normotensive Wistar-Kyoto (WKY) control rats. The growth difference was not due to varying cell survival nor to attachment ability after passage. The degree of DNA synthesis was estimated by [3H]thymidine incorporation into newly synthesized DNA. [3H]thymidine uptake increased with escalating concentrations of calf serum and reached a plateau at 5% calf serum in WKY rats, whereas an excessive, continuous rise was observed in SHR with up to a 20% concentration. [3H]thymidine incorporation into newly synthesized DNA was tested after stimulation by platelet-derived growth factor and epidermal growth factor. A significantly higher amount of newly synthesized DNA in vascular smooth muscle cells from SHR was noted when the cells were stimulated by platelet-derived growth factor or epidermal growth factor alone, and their simultaneous addition did not significantly change the 50% effective concentration but heightened the maximal response. These data provide evidence of increased aortic smooth muscle cell proliferation from aortas of SHR after mitogen stimulation and suggest a defect in growth stimulatory-inhibitory control.