To investigate the role of vasoconstrictor hormones in vascular smooth muscle cell growth we have studied the effects of the potent vasoconstrictor angiotensin II on cell growth in a cultured rat aortic cell model. Angiotensin II was not mitogenic for these cells, as assessed by determining cell number, nor was it synergistic in this regard with 10% calf serum. However, 24-hour exposure to 100 nM angiotensin II caused an 80% increase in protein synthesis (compared with 0.4% increase with serum control) as measured by tritiated leucine incorporation. This was a "hypertrophic" response as indicated by a 30% increase in protein content and a 45% increase in cell volume. Angiotensin II-induced smooth muscle cell hypertrophy was maximal at 100 nM, had an ED50 of 1 nM, and was inhibited by the competitive antagonist [Sar1, Ile8]angiotensin II. The increase in protein synthesis required continuous presence of angiotensin II for 6 hours and required messenger RNA (mRNA) synthesis as suggested by complete inhibition after exposure to actinomycin D. Angiotensin II-stimulated protein synthesis was dependent on a rise in intracellular Ca2+ concentration evidenced by a 70% decrease in tritiated leucine incorporation after chelation of Ca2+ with 25 microM quin 2-AM. This treatment did not alter protein synthesis induced by 10% calf serum. Decreasing extracellular Na+ to prevent Na+/H+ exchange and intracellular alkalinization did not inhibit the angiotensin II response but decreased the 10% calf serum-stimulated protein synthesis by 35%. Downregulation of protein kinase C by 24-hour treatment with phorbol 12,13-dibutyrate did not inhibit angiotensin II-induced protein synthesis, while phorbol 12-myristate 13-acetate-stimulated protein synthesis was abolished. These findings suggest that angiotensin II-induced hypertrophy, acting via a Ca2+ mechanism, may play an important role in abnormal vascular smooth muscle cell growth in certain forms of hypertension.

Berk, B. C., Vekshtein, V., Gordon, H. M., & Tsuda, T. (1989). Angiotensin II-stimulated protein synthesis in cultured vascular smooth muscle cells. Hypertension, 13(4), 305–314.