The sympathetic nervous system (SNS) is commonly activated in hypertension; however, the role of SNS activation in the pathogenesis of cardiovascular structural changes remains poorly defined. In particular, the effect of adrenergic stimulation on extracellular matrix (ECM) protein production by human cardiovascular cells is unknown. The present study thus investigated the direct effect of adrenergic stimulation on ECM protein production by cultured human vascular smooth muscle (VSM) cells. Exposing human VSM cells to norepinephrine increased collagen protein production by 42%, P < 0.01, when compared to control (unstimulated) cells. This effect was mediated by the alpha1-adrenoceptor, since it was inhibited by the selective alpha1-adrenoceptor antagonist; prazosin (2 micromol/l) and reproduced by the selective alpha1-adrenoceptor agonist; phenylephrine (10 micromol/l). In contrast, beta-adrenoceptor stimulation - isoprenaline (1 micromol/l) or norepinephrine (10 micromol/l) + prazosin (2 micromol/l) - inhibited collagen production by 12%, P < 0.01. This inhibitory effect was mediated via the beta1-adrenoceptor, since it was blocked by atenolol (beta1-adrenoceptor antagonist) but not butoxamine (beta2-adrenoceptor antagonist). Fibronectin, another ECM protein, was similarly regulated by alpha- and beta-adrenoceptor stimulation. Transforming growth factor beta1 (TGFbeta1) mRNA expression by human VSM cells was also significantly influenced by adrenergic stimulation, being increased by phenylephrine (alpha-agonist) and inhibited by isoprenaline (beta-agonist). These results uniquely demonstrate the capacity for adrenergic stimulation to directly modulate TGFbeta1 expression and ECM protein synthesis by the human cardiovascular system.