Induction of endothelin secretion by angiotensin II: effects on growth and synthetic activity of vascular smooth muscle cells.

Angiotensin II induces the synthesis and secretion of endothelin by cultured rat vascular smooth muscle cells. Previous studies demonstrate that angiotensin II also activates the synthesis of extracellular matrix-associated glycoconjugates (glycopeptides and proteoglycans) by cultured smooth muscle cells. Furthermore, in culture medium containing mitogen-depleted, plasma-derived serum (1.0%), angiotensin II stimulates the growth of rat smooth muscle cells. Therefore, the influence of endothelin-1 (ET-1) on the growth and matrix elaboration by cultured rat smooth muscle cells was studied to assess its contribution to the stimulatory activity of angiotensin II. In quiescent cultures of smooth muscle cells, no stimulation of the incorporation of [3H]thymidine into DNA by ET-1 was apparent, even at maximal doses (10(-7) M). Under the same conditions, the synthesis of extracellular matrix glycoconjugate material was not enhanced by ET-1, unlike angiotensin II. In cultures maintained in medium containing 1.0% plasma-derived serum, ET-1 was incapable of stimulating either proliferation or incorporation of [3H]thymidine into DNA whereas angiotensin II stimulated both activities. ET-1, however, did induce the expression of growth factor and thrombospondin genes in quiescent smooth muscle cultures. The data suggest that growth stimulation of smooth muscle cells by angiotensin II does not occur as a consequence of stimulated ET-1 production.