ObjectiveThe 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.Methods and resultsExposing 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 α1-adrenoceptor, since it was inhibited by the selective α1-adrenoceptor antagonist; prazosin (2 μmol/l) and reproduced by the selective α1-adrenoceptor agonist; phenylephrine (10 μmol/l). In contrast, β-adrenoceptor stimulation – isoprenaline (1 μmol/l) or norepinephrine (10 μmol/l) + prazosin (2 μmol/l) – inhibited collagen production by 12%,P<0.01. This inhibitory effect was mediated via the β1-adrenoceptor, since it was blocked by atenolol (β1-adrenoceptor antagonist) but not butoxamine (β2-adrenoceptor antagonist). Fibronectin, another ECM protein, was similarly regulated by α- and β-adrenoceptor stimulation. Transforming growth factor β1 (TGFβ1) mRNA expression by human VSM cells was also significantly influenced by adrenergic stimulation, being increased by phenylephrine (α-agonist) and inhibited by isoprenaline (β-agonist).ConclusionsThese results uniquely demonstrate the capacity for adrenergic stimulation to directly modulate TGFβ1 expression and ECM protein synthesis by the human cardiovascular system.