ENDOTHELIN-1 INDUCES AN INCREASE IN TOTAL PROTEIN-SYNTHESIS AND EXPRESSION OF THE SMOOTH-MUSCLE ALPHA-ACTIN GENE IN VASCULAR SMOOTH-MUSCLE CELLS

The growth response of aortic vascular smooth muscle cells (VSMCs) to chronic hypertension includes vascular hypertrophy. We have shown prev iously that angiotensin II positively regulates the expression of the human vascular smooth muscle (SM) alpha-actin gene. To further expand our understanding of vasoactive peptide-induced vascular hypertrophy, we studied endothelin-1 (ET-1) regulation of total protein synthesis a nd cytoskeletal gene expression in VSMCs. In a concentration-dependent manner ET-1 increased [H-3] leucine incorporation by VSMCs (122.4 +/- 5.5%, mean +/- SEM, n = 5). ET-1 (0.1 mu M) induced expression of SM alpha-actin mRNA as detected by Northern blot analysis. Also, ET-1 in a concentration-dependent manner (0.1 nM-0.1 mu M) induced expression of the chloramphenicol acetyl transferase gene driven by 896 bp of the human SM alpha-actin promoter when transiently transfected into rat a ortic VSMCs by the calcium phosphate method (141.2 +/- 9.8%, mean +/- SEM, n = 10). These data suggest that part of ET-1-induced increase in protein synthesis is achieved through transcriptional regulation of t he SM alpha-actin gene via activation of cis-acting element(s) in the promoter. Such findings help elucidate the role of ET-1 in regulation of vascular growth.