Vascular smooth muscle cell effect on endothelial cell endothelin-1 production

Endothelin-1 (ET-1) is a potent mitogen secreted by endothelial cells (ECs) in culture and is a putative factor in vascular lesion development. The pu rpose of this study was to examine whether smooth muscle cells (SMCs) inhib it EC secretion of ET-1. The effect of SMCs on EC ET-1 and constitutively e xpressed nitric oxide (NO) synthase activity was examined by using a bilaye r co-culture model. SMCs inhibited both EC ET-1 protein and RNA levels, com pared with ECs cultured alone. SMCs increased EC NO production when compare d with ECs cultured alone. In addition, SMC inhibition of EC ET-1 productio n could be blocked by the NO synthase inhibitor N-G-Nitro-L arginine-methyl ester. ECs stimulated SMC proliferation, and the ET-1 AB and B receptor bl ockers inhibited EC stimulation of SMC proliferation. The ET-1 A blocker ha d no effect on SMC proliferation. We conclude that SMCs regulate EC ET-1 an d ecNOS synthase transcript levels and protein levels. SMC inhibition of ET -1 production by ECs may be mediated through SMC-modulated changes in EC NO activity. Finally, EC stimulation of SMC proliferation in bilayer co-cultu re is mediated by ET-1 through the ET-1 B receptor.