The amount of NaCl in the diet plays an important role in modulating nitric oxide (NO) synthesis in vivo. In the glomerulus, dietary NaCl also regulates transforming growth factor-beta1 (TGF-beta1) production. We hypothesized that dietary NaCl intake regulated expression of the endothelial isoform of nitric oxide synthase (NOS3) and TGF-beta1 in the aorta. Administration of 8.0% NaCl diet to rats for 7 days did not affect blood pressure but increased steady-state mRNA and protein levels of NOS3 in the arterial wall compared with animals on 0.3% NaCl diet. Northern analysis demonstrated increased steady-state amounts of mRNA of TGF-beta1 in aortas of rats on 8.0% NaCl diet. By ELISA, both total and active TGF-beta1 were increased in these vessel segments. Endothelial denudation of aortic rings reduced active TGF-beta1 secretion to undetectable levels. Addition of a neutralizing antibody to TGF-beta to aortic ring segments attenuated NO production but not to that observed in animals on the 0.3% NaCl diet. The data showed that dietary NaCl intake modulated NOS3 and TGF-beta1 expression in the arterial wall; NOS3 expression was at least partially regulated by endothelial cell production of TGF-beta1.