Mechanism of the enhanced epidermal growth factor-induced growth response of genetically hypertensive vascular myocytes.

Abstract

Although enhanced growth of the vascular myocyte is believed to play a role in hypertensive cardiovascular disease, the cellular basis of altered growth regulation is not completely understood. The present study demonstrates that in the presence of 10% fetal calf serum, the logarithmic growth rate of cultured mesenteric artery myocytes of the spontaneously hypertensive rat (SHR) is similar to that of the normotensive Wistar-Kyoto (WKY) control rat. However, in the presence of low levels of fetal calf serum, SHR myocytes respond to epidermal growth factor (EGF) with increased growth, whereas WKY cells do not. This difference does not result from different numbers or affinities of EGF receptors in these cell lines. Examination of EGF-induced growth responses of SHR and WKY myocytes in the presence of varying levels of insulin or fetal calf serum indicates that, compared with WKY myocytes, SHR myocytes have a lower requirement for factors that confer competence to respond to EGF. Another property of the SHR myocytes is an elevation of free intracellular Ca2+. To determine whether a difference in cellular Ca2+ metabolism might play a role in the differential growth response, growth of myocytes in medium containing 0.25, 0.75, or 1.25 mM extracellular Ca2+ and 5% fetal calf serum was examined. Myocytes of SHR showed enhanced growth in the presence of 5% fetal calf serum at all levels of extracellular Ca2+. It is concluded that, although vascular myocytes of SHR and WKY rats have the capacity to grow at similar rates, under limiting conditions, the SHR myocyte growth response is enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)