The present work was carried out to assess the effect of endothelin on the relative synthesis of protein, RNA, and DNA in confluent rat aortic smooth muscle cells (SMC) derived from Wistar-Kyoto (WKY) rats maintained under serum-free medium in the presence or absence of insulin, transferrin, and selenium. Insulin stimulated protein synthesis by 42%. Endothelin (1 x 10(-7) M) rapidly induced protein synthesis by 22% (-insulin) and 30% (+insulin). Prior treatment of SMC for 4 h with endothelin resulted in 50% (-insulin) and 38% (+insulin) increase in protein synthesis. The stimulatory effect of endothelin on protein synthesis could be partially blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a protein kinase C inhibitor. Atrial natriuretic factor had no effect on either the basal protein synthesis or protein synthesis stimulated by endothelin. Furthermore, endothelin stimulated RNA synthesis by twofold but had no effect on DNA synthesis in SMC derived from WKY rats. In contrast, SMC derived from spontaneously hypertensive rats showed increased DNA synthesis and cell growth after endothelin stimulation. These studies show that this hormone may play a pivotal role in the development of vascular hypertrophy in hypertension.